<SEC-DOCUMENT>0000874015-19-000130.txt : 20191106
<SEC-HEADER>0000874015-19-000130.hdr.sgml : 20191106
<ACCEPTANCE-DATETIME>20191106154216
ACCESSION NUMBER:		0000874015-19-000130
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		70
CONFORMED PERIOD OF REPORT:	20190930
FILED AS OF DATE:		20191106
DATE AS OF CHANGE:		20191106

FILER:

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

	FILING VALUES:
		FORM TYPE:		10-Q
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		191196154

	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 9-30-2019
<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:invest="http://xbrl.sec.gov/invest/2013-01-31" 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/2019-01-31" xmlns:dei="http://xbrl.sec.gov/dei/2019-01-31" xmlns:utr="http://www.xbrl.org/2009/utr" xmlns:num="http://www.xbrl.org/dtr/type/numeric" xmlns:nonnum="http://www.xbrl.org/dtr/type/non-numeric" xmlns:country="http://xbrl.sec.gov/country/2017-01-31" xmlns:currency="http://xbrl.sec.gov/currency/2019-01-31" xmlns:naics="http://xbrl.sec.gov/naics/2017-01-31" xmlns:sic="http://xbrl.sec.gov/sic/2011-01-31" xmlns:stpr="http://xbrl.sec.gov/stpr/2018-01-31" xmlns:exch="http://xbrl.sec.gov/exch/2019-01-31" xmlns:srt="http://fasb.org/srt/2019-01-31" xmlns:ions="http://isispharm.com/20190930" xmlns="http://www.w3.org/1999/xhtml">
<head>
  <title></title>
  <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:EntityRegistrantName" id="Fact_600dd95823ee443a90c01fa60e86a06d" contextRef="c20190101to20190930">IONIS PHARMACEUTICALS INC</ix:nonNumeric><ix:nonNumeric name="dei:EntityCentralIndexKey" id="Fact_df9e30b21d5640d7af3bead6ee6490b9" contextRef="c20190101to20190930">0000874015</ix:nonNumeric><ix:nonNumeric name="dei:CurrentFiscalYearEndDate" id="Fact_5134c462ce0049f1b2d4497db7061298" contextRef="c20190101to20190930">--12-31</ix:nonNumeric><ix:nonNumeric name="dei:AmendmentFlag" id="Fact_f8436eb51608482a9a51314ed579886f" contextRef="c20190101to20190930" format="ixt:booleanfalse">false</ix:nonNumeric><ix:nonNumeric name="dei:DocumentFiscalYearFocus" id="Fact_ac6e42fd003745c7bb97630febb71ac5" contextRef="c20190101to20190930">2019</ix:nonNumeric><ix:nonNumeric name="dei:DocumentFiscalPeriodFocus" id="Fact_2790ecf0636d4ade949ac83e617495b0" contextRef="c20190101to20190930">Q3</ix:nonNumeric><ix:nonNumeric name="ions:PeriodAfterBillingWhenPaymentIsReceived" id="Fact_1b180806199c40a58d73092447ceea40" contextRef="c20190101to20190930">P3M</ix:nonNumeric></ix:hidden><ix:references><link:schemaRef xlink:href="ions-20190930.xsd" xlink:type="simple"></link:schemaRef></ix:references><ix:resources><xbrli:context id="c20190101to20190930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20191031"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2019-10-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190630_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630_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>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231_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>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630_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>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231_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>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231_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>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630_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>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630_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>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630_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>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630_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>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20171231_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>2017-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630_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>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180630_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630_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>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180930_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>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180930_StatementEquityComponentsAxis_ParentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180930_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>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180930_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>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180930_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>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2017-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20191001to20191231_OwnershipAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:StatementScenarioAxis">srt:ScenarioForecastMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-10-01</xbrli:startDate><xbrli:endDate>2019-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190401to20190630_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-04-01</xbrli:startDate><xbrli:endDate>2019-06-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:IONISLRRK2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2017-02-01</xbrli:startDate><xbrli:endDate>2017-02-28</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2015-05-01</xbrli:startDate><xbrli:endDate>2015-05-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</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="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-04-01</xbrli:startDate><xbrli:endDate>2019-06-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20170228_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBayerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2017-02-28</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2017-02-28</xbrli:instant></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="c20170731_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2017-07-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180430_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-04-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190331_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AdjustmentsForNewAccountingPronouncementsAxis">us-gaap:AccountingStandardsUpdate201602Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_RestrictedStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_AwardTypeAxis_RestrictedStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180930_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>2018-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><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="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_EmployeeMember"><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="us-gaap:RelatedPartyTransactionsByRelatedPartyAxis">ions:EmployeeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_BoardOfDirectorsMember"><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="us-gaap:RelatedPartyTransactionsByRelatedPartyAxis">ions:BoardOfDirectorsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190531_PlanNameAxis_EquityIncentivePlan2011Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PlanNameAxis">ions:EquityIncentivePlan2011Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-05-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190630_PlanNameAxis_EquityIncentivePlan2011Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PlanNameAxis">ions:EquityIncentivePlan2011Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-06-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_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>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_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>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_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>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_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>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190901to20190930"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2019-09-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentTypeAxis_DebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentTypeAxis_DebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"><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:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"><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:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"><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:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180101to20181231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_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:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_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:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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:FairValueInputsLevel3Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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: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:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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:FairValueInputsLevel1Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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: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:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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: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:FairValueInputsLevel1Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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: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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_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:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</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>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_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: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>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_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:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceSubleasedToAkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceSubleasedToAkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceForCorporateHeadquartersMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceForCorporateHeadquartersMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</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="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><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:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><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:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-04-01</xbrli:startDate><xbrli:endDate>2019-06-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentServicesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_ProductOrServiceAxis_IONISMAPTMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:IONISMAPTMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentServicesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20191001to20191031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:SubsequentEventTypeAxis">us-gaap:SubsequentEventMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-10-01</xbrli:startDate><xbrli:endDate>2019-10-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MinimumMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:LicenseMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><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:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MinimumMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:AKCEAAPOALMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190331_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:AKCEAAPOALMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><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:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><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:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:SubsequentEventTypeAxis">us-gaap:SubsequentEventMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-10-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20191001to20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:SubsequentEventTypeAxis">us-gaap:SubsequentEventMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-10-01</xbrli:startDate><xbrli:endDate>2019-10-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:StatementScenarioAxis">srt:ScenarioForecastMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-10-01</xbrli:startDate><xbrli:endDate>2019-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember"><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><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember"><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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-01-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-07-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-01-01</xbrli:startDate><xbrli:endDate>2018-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_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><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2019-07-01</xbrli:startDate><xbrli:endDate>2019-09-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_ConsolidationItemsAxis_IntersegmentEliminationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2018-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2019-09-30</xbrli:instant></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:PerformanceObligation</xbrli:measure></xbrli:unit><xbrli:unit id="U006"><xbrli:measure>ions:Agreement</xbrli:measure></xbrli:unit><xbrli:unit id="U007"><xbrli:measure>ions:Company</xbrli:measure></xbrli:unit><xbrli:unit id="U008"><xbrli:measure>ions:Segment</xbrli:measure></xbrli:unit><xbrli:unit id="U009"><xbrli:measure>ions:Officer</xbrli:measure></xbrli:unit><xbrli:unit id="U010"><xbrli:measure>ions:Investment</xbrli:measure></xbrli:unit><xbrli:unit id="U011"><xbrli:measure>ions:Option</xbrli:measure></xbrli:unit><xbrli:unit id="U012"><xbrli:measure>ions:Medicine</xbrli:measure></xbrli:unit><xbrli:unit id="U013"><xbrli:measure>ions:Payment</xbrli:measure></xbrli:unit><xbrli:unit id="U014"><xbrli:measure>ions:Target</xbrli:measure></xbrli:unit><xbrli:unit id="U015"><xbrli:measure>ions:Drug</xbrli:measure></xbrli:unit><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_138aaf4a47a148d091cceb4ced2e1cfc" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_ea15651e08bd4b8b990074a9aa80683d" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_206242051e2c4d94b28d4e87712895a7" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_f4c2236cedf849b8971016981b4f39e6" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_bed56c4d2fcd4a74a0a1ccb2d57c9639" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_9801fd693cf84c299d17cb204de46d5f" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_248f6769580b4861a0b529d0816594e0" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_78a409a549ef459db614b179f7ae1230" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_f4ce593384ef4b7d83aad4901d4548b6" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_80f9e07c881d4103821ad1c51c0e34b7" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_0187b54b654f4e109666c7737fc2551d" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_9015169599984f5a9691efcc7214ed32" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_15869a0e101243b38f48dfa9071509af" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_cb912863d431429d957f3c945ccb7b83" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_5bd44b202ba0488e976f0c108e51d72a" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_9339c651e1c64d02a58d7ef8f3a401fa" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_eab544f46afa456189480b40679240a9" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_2536445b56a5427d99424937cbc97ea6" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_1c044e91f5e742a3961b4f59ca6ef285" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_1f3e39cc38284f8aad73189eea7bbf14" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_9f527800450b4ccfad702bd8b0ced078" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_b181ed8da53647f8a6b292342a235f93" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_a40f4d8491b24020962dbd41df0b3f94" toRefs="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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_5bd44b202ba0488e976f0c108e51d72a" 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_1c044e91f5e742a3961b4f59ca6ef285" 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_1f3e39cc38284f8aad73189eea7bbf14" 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_005ea5438f1a425e8a7d2f6ca3f789f8" 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_26191d5384f64272905581a8fe8b850e" 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_d2cf55f51c9147beb6d1c06acf8ed2dc" 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_31607d0464414d63a9d40c3bda86cebd" toRefs="Foot_e555e136aa274c8e882586614fcdf5b2" 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_cf2cd8ea24c34a298b35a62e5c63fe49" toRefs="Foot_e555e136aa274c8e882586614fcdf5b2" 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_719745a58a2745968c9eec989ba98101" toRefs="Foot_e555e136aa274c8e882586614fcdf5b2" 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_303ee7acffb64b30b37958792583e02d" toRefs="Foot_e555e136aa274c8e882586614fcdf5b2" 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_d28150ca7b45448fa25fbb6cd2de43d0" toRefs="Foot_e555e136aa274c8e882586614fcdf5b2" 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_7e9a01d143344a90abd0d3c282087ea8" 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_6e8ff7ac339a47ee87988299df92fe42" toRefs="Foot_f21495f28c8740a99946dade31b02bd8" 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_57ccf9920b8146f388ce592d258d1e8f" 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_3e8681d673cb4651bd1fa1b44eaab381" 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_1f42a3296a8a46159ca5daccd95f28b8" 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_8433f3b9512246ac8207c5a05c776b60" 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_48764182e11a4bb5958ad2aaafc3c0c6" 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_df377b1e9061452b8f3d582001e6a515" 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_3068d59045b74301b2c28fc3dfb6b8be" toRefs="Foot_550ffd62f7c940f1b6c1073473427cdb" 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_fbe5ecbb80b44b659c35900b4d87399c" toRefs="Foot_f913e9fa94634b87a1ff2c11bfad2e80" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship></ix:resources></ix:header></div>
<div></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%0%%%--><hr style="border: none; border-bottom: 1px solid black; border-top: 4px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;" />UNITED STATES</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;">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_9fcd2cdb7eb04c178e9dd2ab1d03f020" contextRef="c20190101to20190930">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>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zf74054de88ea4e6a8a458e9498414011">
  <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_4402cd610e3c4c7784fbd9a7ad693bc7" contextRef="c20190101to20190930" 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>
</div>
<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_2b97f8d9ccd74e52bd2a1ad2ca28adbe" contextRef="c20190101to20190930" format="ixt:datemonthdayyearen">September 30, 2019</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>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z98386deed9214d4bb4ea89d13dae09fc">
  <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_dfb67515b57d446fbfa4cdfed68e05ec" contextRef="c20190101to20190930" 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>
</div>
<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_3e579d3aafdc4090b092fe8d3c101f8e" contextRef="c20190101to20190930">000-19125</ix:nonNumeric></div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zd2dbbc6359e2419fa6237e0d67b4f046" 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;"><span style="-sec-ix-hidden:Fact_600dd95823ee443a90c01fa60e86a06d">Ionis Pharmaceuticals, Inc.</span></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;" id="zda56d302d2d74d9bb4c7e1e3b493b333">
  <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_293ac86583764385aa6d4d3384929ec4" contextRef="c20190101to20190930" 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_5da20f5de6c54bc5aa8f25908e78486e" contextRef="c20190101to20190930">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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br /></span>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;" id="z3cdb6acacf1f471bb4a58edea7a5c670">
  <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_172771314c0d4f939bacbbddd3388314" contextRef="c20190101to20190930">2855 Gazelle Court</ix:nonNumeric>, <ix:nonNumeric name="dei:EntityAddressCityOrTown" id="Fact_e9acebb9c7d2485495774f21d9f8edba" contextRef="c20190101to20190930">Carlsbad</ix:nonNumeric>, <ix:nonNumeric name="dei:EntityAddressStateOrProvince" id="Fact_2920ce073ddc4ae18ab93dda07f49d47" contextRef="c20190101to20190930" 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_767de21bf7d24e0dbb420c77385846e3" contextRef="c20190101to20190930">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_2dc9c533eea043b58d89bf1ec803479b" contextRef="c20190101to20190930">760</ix:nonNumeric>-<ix:nonNumeric name="dei:LocalPhoneNumber" id="Fact_9ffb5548083a43c28a9f8b7807388cbc" contextRef="c20190101to20190930">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; margin-top: 6pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities registered pursuant to Section 12(b) of the Act:</div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zda3f91853940488d84c1a50a5aefb350">
  <tr>
    <td style="width: 29.17%; 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: 2.57%; vertical-align: top;">&#160;</td>
    <td style="width: 36.55%; 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>
    <td style="width: 3.33%; vertical-align: top;">&#160;</td>
    <td style="width: 28.38%; vertical-align: top; border-bottom: #000000 2px solid;"><div>&#160;</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trading symbol</div></td>
  </tr>
  <tr>
    <td style="width: 29.17%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:Security12bTitle" id="Fact_cef7ebd4a9374d22b9707aabeedac92f" contextRef="c20190101to20190930">Common Stock, $.001 Par Value</ix:nonNumeric></div></td>
    <td style="width: 2.57%; vertical-align: top;">&#160;</td>
    <td style="width: 36.55%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:SecurityExchangeName" id="Fact_63e7e94cd180424c9970da0211c88bec" contextRef="c20190101to20190930" format="ixt-sec:exchnameen">The Nasdaq Stock Market LLC</ix:nonNumeric></div></td>
    <td style="width: 3.33%; vertical-align: top;">&#160;</td>
    <td style="width: 28.38%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;<ix:nonNumeric name="dei:TradingSymbol" id="Fact_e08c5f4a91b441a98bdeb1c688d2dc6a" contextRef="c20190101to20190930">IONS</ix:nonNumeric>&#8221;</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>
<div style="text-align: left; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Securities registered pursuant to Section 12(g) of the Act: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">None</span></div>
<table cellpadding="0" cellspacing="0" id="z7e82336657a249a1b8dd1ee5f09db1f3" 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_eee89e18b8d947ef8eaa32cab0408571" contextRef="c20190101to20190930">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 and posted on its corporate Web site, if any, 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 and post such files). <ix:nonNumeric name="dei:EntityInteractiveDataCurrent" id="Fact_8390f7c177c04c5bbb8d0bd5eddf56e2" contextRef="c20190101to20190930">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. (Check one):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zc1073fbf3a0042f7ba20542aac13e6d2">
  <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_31428acaf33441f0beadbf17b6c02814" contextRef="c20190101to20190930">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_ebbd406b283b4f998d5cefdb153525c0" contextRef="c20190101to20190930" 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_5628b90d7c6644c2b1bff035392709df" contextRef="c20190101to20190930" 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 7(a)(2)(B) of the Securities Act. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_e031ce3131bb4775b45521bee2ee7e85" contextRef="c20190101to20190930" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></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_491fd78eaea544c9ab3f3335b0fb5df4" contextRef="c20190101to20190930" 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 October 31, 2019 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_a0521e2fdc4644ee9ab0f0386210b487" contextRef="c20191031" unitRef="U001" decimals="INF" scale="0" format="ixt:numdotdecimal">140,663,254</ix:nonFraction>.</div>
<div><br /></div>
<div>
<div><br /></div>
</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
</div>
<div></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><!--PROfilePageNumberReset%Num%2%%%--></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORM 10-Q</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zc3da18a64e214c0c805142ab8beab5e3">
  <tr>
    <td style="width: 8.92%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I</div></td>
    <td style="width: 83.07%; vertical-align: top;"><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: 8.01%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1:</div></td>
    <td style="width: 83.07%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial Statements:</div></td>
    <td style="width: 8.01%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Balance Sheets as of September 30, 2019 (unaudited) and December 31, 2018</div></td>
    <td style="width: 8.01%; 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: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Operations for the three and nine months ended&#xA0;September 30, 2019 and 2018 (unaudited)</div></td>
    <td style="width: 8.01%; 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: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Comprehensive Income (Loss) for the three and nine months ended&#xA0;September 30, 2019 and 2018 (unaudited)</div></td>
    <td style="width: 8.01%; 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: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Stockholders&#8217; Equity for the three and nine months ended&#xA0;September 30, 2019 and 2018 (unaudited)</div></td>
    <td style="width: 8.01%; 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: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Cash Flows for the nine months ended&#xA0;September 30, 2019 and 2018 (unaudited)</div></td>
    <td style="width: 8.01%; 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: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Notes to Condensed Consolidated Financial Statements (unaudited)</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 2:</div></td>
    <td style="width: 83.07%; 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: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; 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;">Overview</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Results of Operations</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liquidity and Capital Resources</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quantitative and Qualitative Disclosures about Market Risk</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 4:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Controls and Procedures</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; 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: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OTHER INFORMATION</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Legal Proceedings</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; 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: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk Factors</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 2:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unregistered Sales of Equity Securities and Use of Proceeds</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Default upon Senior Securities</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 4:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mine Safety Disclosures</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 5:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other Information</div></td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54</div></td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.92%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 6:</div></td>
    <td style="width: 83.07%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</div></td>
    <td style="width: 8.01%; 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: 8.92%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 83.07%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td colspan="2" style="width: 91.99%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">SIGNATURES</div></td>
    <td style="width: 8.01%; 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>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>"Ionis," the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this report are the property of Ionis Pharmaceuticals, Inc. "Akcea," the Akcea logo, and other trademarks or service marks appearing in this report, including TEGSEDI (inotersen) and WAYLIVRA (volanesorsen), are the property of Akcea Therapeutics, Inc. This report contains additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and trade names referred to in this report may appear without the &#174; or TM symbols.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>2</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED 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" id="zf32af87a730a420a882aa52b61f21524" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="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;">September 30,</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 4.5pt;">December 31,</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;">&#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><div> </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="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">247,939</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">278,820</ix:nonFraction></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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_05d3c63942424d44b3a45d0e399d7509" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,972,891</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_40b92a7d67634da98603b4b62a18fd2a" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,805,252</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">49,077</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,759</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: 76%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_bdc1851ec3a24426938e66ad4005713a" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,375</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_efd195f3edec4c3091ff79a53462abb8" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">8,582</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">118,809</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="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">102,473</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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsCurrent" id="Fact_4a277ae70920496a859de16b126a781a" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,408,091</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsCurrent" id="Fact_e034b0a9b6284d72a53c220d22bd9ae4" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,207,886</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">148,717</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">132,160</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsNet" id="Fact_edce7eb26c0445978fe4ae3f9eed3d07" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,985</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:FiniteLivedIntangibleAssetsNet" id="Fact_7f0d3ff8c03f42ccb4e063d20c964f58" contextRef="c20181231" 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%; background-color: #FFFFFF; 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 tax assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNetNoncurrent" id="Fact_27b7fc0a3c4943289d67893d78760afc" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">284,997</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNetNoncurrent" id="Fact_b78601c074a24e579332fef12795e70d" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">290,796</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deposits and other assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsNoncurrent" id="Fact_d40d8e0c343c4faa8c8a1998eaa5093e" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,199</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsNoncurrent" id="Fact_20e82d483df24cd682d948f6abcde7a0" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,910</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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 assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:Assets" id="Fact_e57f61237ed14bad8578d2b47564ba8a" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,894,989</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:Assets" id="Fact_bacec939ac84418cbf35df017212761d" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,667,784</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><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%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts payable</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:AccountsPayableCurrent" id="Fact_e36e66d0552f404099023f535d194dfe" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">13,146</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:AccountsPayableCurrent" id="Fact_0c0b6424e746450abd937b9f839aed88" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">28,660</ix:nonFraction></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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_552968f4f2a9496e83f175a2ee89b95c" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,404</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_e06d0b21026d4d1db2ff5f69431f6629" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">29,268</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_2fefcdea93734fcd9274bd7403d639f5" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">52,615</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_213f5a6701c24aa0979bad8e60ab97c3" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">47,503</ix:nonFraction></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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_2af0ce9cd98b44bd81fc94205bb5c219" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,945</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_7acc385f5ade40c4a52676f52d77facb" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">858</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current portion of long-term obligations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent" id="Fact_bfee8ed3f29a415ba60a766b5e0cc4b7" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,060</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent" id="Fact_41e0bc055640457ebe9012a9d8313b03" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">13,749</ix:nonFraction></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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_09d676ed2f6648e5b73076a656df1277" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">137,607</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_0b483c68b6994735bd21436d4b811df6" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">160,256</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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 current liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_b563c92d4e8b4add87b63f57c52a0e82" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">231,777</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesCurrent" id="Fact_d521a592d7c446a7b398adb17b375e32" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">280,294</ix:nonFraction></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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityNoncurrent" id="Fact_8aa6408241e44715ba99551864adcae8" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">492,979</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityNoncurrent" id="Fact_ede8dfed22c34e9582c277c64ee5a671" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">567,359</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_bbd023eee50e42438aa37192e3fb599a" contextRef="c20181231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3d6e1ab8d0ea4dfca582273a77b28bd5" contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></ix:nonFraction> percent convertible senior notes</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_74ce7adcfde44543a313ce009163795e" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">596,355</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_18f77ca1d76f433882b17b855d930dd6" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">568,215</ix:nonFraction></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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term obligations, less current portion</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_29af6f780a0e49fdbb18e694cd1336d7" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,016</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_633c4e81bd56468da5eab170b086f121" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,914</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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_47ee861cba2b4ba3b4ea02fec4ccb666" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,896</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_aa0760afbb9c4732aa47a17bbf801618" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,842</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_d80c046b930b4bbc9a617d5de07fbac7" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,397,023</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_90063554b014412d8b997e613766a9b5" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,480,624</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common stock, $<ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_89ceac2a6de84664a3444e0197c5952f" contextRef="c20181231" unitRef="U004" decimals="3" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_81d34c4177db42eb9566a4ebacfe9a61" contextRef="c20190930" unitRef="U004" decimals="3" scale="0" format="ixt:numdotdecimal">0.001</ix:nonFraction></ix:nonFraction> par value; <ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_c1d115fce5ca4643b306e1dda169e403" contextRef="c20181231" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_967e3bfa845149deb2a16ff5f6733824" contextRef="c20190930" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">300,000,000</ix:nonFraction></ix:nonFraction> shares authorized, <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_7433a63c4a1045d2ab18a5f4dd2cfef3" contextRef="c20190930" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_aeabe9bc47984305a06e132d4d7bbbd3" contextRef="c20190930" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">140,636,397</ix:nonFraction></ix:nonFraction> and <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_16b1e67a7f564bfb8ebe67a950cecb91" contextRef="c20181231" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_987e70eb15fa4d6f8f4dee73a63054d5" contextRef="c20181231" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">137,928,828</ix:nonFraction></ix:nonFraction> shares issued and outstanding at September 30, 2019 (unaudited) and December 31, 2018, respectively</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_b41f780321ff493f897af65f3a6e39be" contextRef="c20190930" 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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_1fc75883a1c54dde89dbf7d834d50fb8" contextRef="c20181231" 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: #FFFFFF; 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_f460fecc10794c159f5558f0e607190e" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,219,090</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_11b21d76e415443eacd46443135bee23" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,047,250</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated other comprehensive loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_0fa166eb9bd4465a9b655bbddbbc9660" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25,375</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_aaa97c5af992480997806ad6ed39c8b8" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,016</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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_b87fd4221ecc4c9dbc01611589c1f02d" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">857,563</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_70969fab8ec04e7583d69d70666445de" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">967,293</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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Ionis stockholders&#8217; equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_f7df6d935cfc498584c42c103121920f" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,336,293</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_796dd0d0c977460fa5f2ab16e5545e4b" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,048,079</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;">&#160;&#160;&#160;Noncontrolling interest in Akcea Therapeutics, Inc.</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:MinorityInterest" id="Fact_0e8547099dcc477d9574551822f8c2cc" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">161,673</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:MinorityInterest" id="Fact_5ab17487f86d49fa8f57d80fc26134da" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">139,081</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; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders&#8217; equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_19cb4d43fab24662ad8de75f93f0f483" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,497,966</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6951ed54246642938032f494c08fdf05" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,187,160</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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_134e1347f8c347aab0132349b4784b81" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,894,989</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_49524665a65e4e5db0c98d6bb79422df" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,667,784</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>3</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands, except for per share amounts)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z9d32288b94bc40008bd27510f3d65d59" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; 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>
    <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>
    <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: -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_0b7e92ae84094d37aed4349f19fe764e" contextRef="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">81,672</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_82fd59906fb44bf4b175b6e556a27aac" contextRef="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">70,010</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_fc05c9c21bbd4d598e399567bd0f844d" contextRef="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">211,884</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_9e31bec432124f7c8f83a4f356e361da" contextRef="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">167,743</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_666782232adc4d97b1de7acd7fe4af26" contextRef="c20190701to20190930_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,945</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6d53ba73214c4912b0f063f1483c62c1" contextRef="c20180701to20180930_ProductOrServiceAxis_ProductMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c692e5012c26423f8d5dbd3a8094950e" contextRef="c20190101to20190930_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">28,563</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3fbd588a01cd48839b4bfc40a134670e" contextRef="c20180101to20180930_ProductOrServiceAxis_ProductMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -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%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_5be3788d99f54fdfaee577a7cda5700b" contextRef="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,082</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_0347f12cd3584a27a5619a2467dd39b0" contextRef="c20180701to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,746</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_2ca205ab66e94f488dbfed885dd2ec26" contextRef="c20190101to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,638</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_1e01b330b4b0472c9250121ed807739a" contextRef="c20180101to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,232</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_271ba182566f4bc190d8233a71995d31" contextRef="c20190701to20190930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">95,699</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_11a881c1e93e430eac6f59cbf9c4736b" contextRef="c20180701to20180930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">82,756</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3390343e9af54d66a37bc2b71ebdada1" contextRef="c20190101to20190930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">252,085</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ea548ed659af43b48bb282d83609fa0b" contextRef="c20180101to20180930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">181,975</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue under collaborative agreements</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_8fd333eb68924256a711503ecfe6689a" contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">72,193</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_19de1dac977a4ba5974be8c2aac9440b" contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">62,639</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_fa04642ad0d24d40b948016a1d2e427c" contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">376,833</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_b5f0d20ca299467388d20dd594b8c246" contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">225,584</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fc7abdc8dfde471cb29faf8b3d03b1e5" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">167,892</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d18c45e0616c4b608bc566221c7d5133" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">145,395</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ea3d788d8e4c4ca49f0e56246a6353d6" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">628,918</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_946194dd265d4cea91b3510e10eec2e5" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">407,559</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of products sold</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostOfGoodsAndServicesSold" id="Fact_c4ea9d289db04074bad2be0b780555ef" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">967</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostOfGoodsAndServicesSold" id="Fact_3f378c9d048d4d0abe6a570fd9323df7" contextRef="c20180701to20180930" 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:CostOfGoodsAndServicesSold" id="Fact_c2742b31d05445a1895276df6ff2c638" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,373</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostOfGoodsAndServicesSold" id="Fact_dbe88d486cf14375a9f138d6c30834d5" contextRef="c20180101to20180930" 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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ResearchDevelopmentAndPatentExpense" id="Fact_a9acfc8017e7443cadb09efb73dd40aa" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">104,366</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ResearchDevelopmentAndPatentExpense" id="Fact_5ec7677070de41efba668575300cbc3b" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">95,255</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ResearchDevelopmentAndPatentExpense" id="Fact_6c53d68927644fc5908dc607a0f004fb" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">316,948</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:ResearchDevelopmentAndPatentExpense" id="Fact_aadd9a4a9b6e45d396e8e9c8d975c3a8" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">301,153</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 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; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SellingGeneralAndAdministrativeExpense" id="Fact_88509240b8f44a01a221693c1c02bb2a" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">60,036</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SellingGeneralAndAdministrativeExpense" id="Fact_16ecfb44722848e38992eb9ca9030a3f" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">68,712</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SellingGeneralAndAdministrativeExpense" id="Fact_054cd1ab95374ebd8869d776879a9740" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">203,368</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SellingGeneralAndAdministrativeExpense" id="Fact_2ff4a991cea4496b884cbe0856914388" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">178,563</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_2475cd3acfd24e6cbbc308e4c9e591b9" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">165,369</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_ad210a86a31a424e9965b4608c3fe4e5" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">163,967</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_aa6c4d98b6394cbe8ccd0ee6c8cebd19" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">523,689</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_4fbf0fcf0f4142b1b4afedb23bae57ad" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">479,716</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_bee2844586ba438c8e913f61b67d695a" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,523</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_0c2223c913e04fa7a54624202a8f288f" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">18,572</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_76aedfc468a64cb7aef3f084651fb9b9" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">105,229</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_d1d46d66a90149e5b13f260102617cfd" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">72,157</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other income (expense):</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_66c58aa0cc1149b793eab1f8666cea91" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">13,136</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_f1678e81b9bb4a9d973cf0e5d0aa3275" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,963</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_0d64264f32b4486b894513e64aff02d3" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">39,015</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InvestmentIncomeNet" id="Fact_cbd13fb3278b42f4af046675f6407585" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,711</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_54aac10cb0064fbe92e0fba8afd6804a" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,002</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_718aef5f4e5c47ed993b6dc62100e496" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,282</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_2e8326e1dfff4b1ea6081f53587960f9" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">35,404</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_99b07d066f7e4ca98c5bff25af703b10" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">33,332</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other income (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:OtherNonoperatingIncomeExpense" id="Fact_01fdf07252e54f319cb90db79a32d5d0" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">140</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#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_1175fa808fa6467fa69c45f4c6ffb802" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">22</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:OtherNonoperatingIncomeExpense" id="Fact_14d3f9e37db043e9b6e9051b02cb728d" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">332</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:OtherNonoperatingIncomeExpense" id="Fact_fa874df28ad34f8db61bd85baa7b2b8f" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">145</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: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Income (loss) before income tax (expense) benefit</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" id="Fact_4e15511699034f4d9b1ebe90cebb3ff3" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,517</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" id="Fact_ae656811157844b5ba3ea60d95c6c011" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">19,913</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" id="Fact_96b769f3a1e94075b08c9a9c0a99b7ab" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">108,508</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" id="Fact_0fd4ef6b1fc94874a6d21469662158c7" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">86,923</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: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Income tax (expense) benefit</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_8ce8cdd30acf4bbc839e7536c1a25e45" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">14,915</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:IncomeTaxExpenseBenefit" id="Fact_391c23bb87034306903c5e329f247717" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">452</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_69f39ebeb04d480ba5b5698dbb3a8275" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,204</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_4ce3fbd20b7e46459a27754ecad5863a" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">824</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: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Net income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_6e839ad01bca473db272756ca24f0c6c" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,432</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_4a3cf63ebc8c4917ba22720d153c34e6" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">20,365</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:ProfitLoss" id="Fact_a05a0daeca784f1085c298eda7c00b97" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99,304</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_0fbef789f1334a9086f868678bb389ab" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">87,747</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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:NetIncomeLossAttributableToNoncontrollingInterest" id="Fact_9880bcb6013f487caf2824136dbb2aad" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,732</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:NetIncomeLossAttributableToNoncontrollingInterest" id="Fact_032762f55fd243a6b68fb4543524a1d8" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">15,806</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:NetIncomeLossAttributableToNoncontrollingInterest" id="Fact_d57908ccdd8247a382987a2800dacce3" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">10,426</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:NetIncomeLossAttributableToNoncontrollingInterest" id="Fact_bf4aef66191d47af85daec16883e4386" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">41,412</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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_e3073c5f38e04ff596a4331d93107ae6" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,163</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b31821fc458d431999aec86855835cd4" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,559</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_3337df5280e143d4bf6b2ee0bc26ca21" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">109,730</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:NetIncomeLoss" id="Fact_b83dbcd82d4846cdbdbb049adc53fbe8" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">46,335</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: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income (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:EarningsPerShareBasic" id="Fact_5fc4c4e19798409a922b541c2e74e551" contextRef="c20190701to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.19</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_3a0c2f544ba54492bba4f602b2c20f5c" contextRef="c20180701to20180930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.03</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:EarningsPerShareBasic" id="Fact_87f607dd11724c82a75bf67ec6bc0726" contextRef="c20190101to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.81</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:EarningsPerShareBasic" id="Fact_ebc5b8c1d1774c90a2eed601a46d5092" contextRef="c20180101to20180930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.33</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: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares used in computing basic net income (loss) per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_413750ca99dd490aabc1f5ce044c7bd2" contextRef="c20190701to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,551</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_89ae87d3ce154c29b80ab797905a4335" contextRef="c20180701to20180930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,346</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_cf5a3286afeb4ba091732f9659f005a0" contextRef="c20190101to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">139,800</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_86db24f4e52b47c3ae8b79a4eee6c5a7" contextRef="c20180101to20180930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">130,507</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net income (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_de8dfc22ca3346229ea5ae768a2fae60" contextRef="c20190701to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.18</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_a6389f538da2442cbfd16ab66ce3ba4e" contextRef="c20180701to20180930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.03</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_540ef4013fa04ee6a485bb76536d6f72" contextRef="c20190101to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.79</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:EarningsPerShareDiluted" id="Fact_e9745ef5d64d4dcb82f0afe9ae660902" contextRef="c20180101to20180930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.33</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: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares used in computing diluted net income (loss) per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_d49d301e3cc945869aec44ece6cbad37" contextRef="c20190701to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">143,408</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_bf0aedc97af44714af5336a371515cc8" contextRef="c20180701to20180930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,346</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_f48d610147fa4ae1a37ac7a3d9e37c31" contextRef="c20190101to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">142,821</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_e8ed2d920fd0439b9a5d8732eec0f5ff" contextRef="c20180101to20180930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">130,507</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>4</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zdd6ff26d1b0a4df79406ddae9a852491" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;">&#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>
    <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;">Net income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: '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:ProfitLoss" id="Fact_956abcf640b64e40a411493d69205818" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,432</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_47e41b95caab4e92bb28995bd44b3aad" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">20,365</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:ProfitLoss" id="Fact_8300a6f66bfe443db38d77ca66f51505" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99,304</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:ProfitLoss" id="Fact_23d6e30666fb4b788e6dd4f69f822c31" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">87,747</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on debt securities, net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_55347736030740569e680a5e37637b63" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,110</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_d74b567e3b014156a049c64e1307a63a" contextRef="c20180701to20180930" 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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_a0e0ce1af3e4453cb56c625c0c8f2800" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,666</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_a5e1f7fa552a425a9c7bfb376af815b6" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">834</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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;">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_e9b531ac4e7e466f809b4e8a0d95361e" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">13</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_b162ec084f6c46ccaef6685d9c1854ba" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">31</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_a20a0cc52121458bb55a81fdd00e75b7" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25</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_daa1a7f93f5945139be6141a4e1ef612" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">61</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Comprehensive income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_f0bdb8167ba5440599f8ff8f4600c9fe" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">17,309</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_1d9694905eb840a7a1ca80fb0815c33e" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">20,263</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_be0067f854be45bf95bdf2c489e2d13e" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">105,945</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_f317117367b0435c862ef7858aad4a56" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">88,520</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: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Comprehensive loss attributable to noncontrolling interests</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:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_a269dc621aa04d119bef4f51cfd30b55" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,729</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:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_8cb081eaec8d4a1ba90652e3efc63cd6" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">13,943</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:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_6ae3051280094a839a54335e64d62821" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">10,423</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;"><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:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_1605d18c25544e4a82d222c9f7bc9a9b" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">38,005</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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_065f79ada0374820bc5a6fbec88a7615" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">25,038</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_7959aba910af49989a21445262c14dde" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">6,320</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_4ef4b46b1e6548a9989d6308f38d02ec" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">116,368</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:ComprehensiveIncomeNetOfTax" id="Fact_d9ab0bf4afe247139adf3c7fd48dcc8f" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">50,515</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;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>5</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> EQUITY</span></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended&#xA0;September 30, 2018 and 2019</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zfddf74bad8fa443dbf966695fcce80dc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 Ionis</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div></td>
    <td 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;">Noncontrolling</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Interest in Akcea</div></td>
    <td 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; 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;">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>
    <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;">Therapeutics, Inc.</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: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at June 30, 2018</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_bceab59188424c15adeaa4abc2b75b2c" contextRef="c20180630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,157</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_f88139526b6546c0a62ece28db065504" contextRef="c20180630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">137</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_78cf6c31b63d4529a7b11529d0d3fac7" contextRef="c20180630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,011,561</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_47ae58c233e44842bafc4d977a4aa088" contextRef="c20180630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,634</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_7c0e43df67e14da49a468b8edca8b7ed" contextRef="c20180630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,282,810</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6c3bdff0323a479bbc545417e99af981" contextRef="c20180630_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">696,254</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_596d88f5d89942a69c32fb0dc5d059e3" contextRef="c20180630_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">121,181</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_c06694f9fb0b4755a570468320903574" contextRef="c20180630" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">817,436</ix:nonFraction></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: 20%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_9fc566f7fda04ae5a5c8ea2305bdf298" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_bb24e7d634c44db38ea3ffa53ac03797" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_e9359509cd5a439e82e79b016c1fab7f" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_4b4f5c2aabf34cefaa88539842c518da" contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,559</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_156717fab30449c1b5eacac23304af91" contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,559</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_44a7c5e4da9e43f09944151b7a453391" contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3158a0f067284faeb554dcb4f6ce5ef2" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,559</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains (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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_593e345ebaae46dbb963d490969b01b6" contextRef="c20180701to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_eac9065025fe450a9a08f92abe49d5ca" contextRef="c20180701to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_f4951a777dc447b58af150fdb4dca2fa" contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7a2b7d1f5d4b4cf2b6bbdf306650d93d" contextRef="c20180701to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_95d55e206caa47b1a446bf9db36d287c" contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_2965ef559b3c4d84ae8ecd3e0783ff50" contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_b214c0c8476b4d219a6cf92692b53f88" contextRef="c20180701to20180930" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e29f8ebcc2f0483a9440f01323ea3e11" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_821accc58f9145f3b1740e74ff0af16f" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_bacfd0c31c3e429391016b2bc472d382" contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">31</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_fd2bb27765944367b3078298024899ee" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_a439436ef2774a7985521c51bf62a03d" contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">31</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0cf82e5935704d11904efa4267b6229e" contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_6360ce93a0d54280815c7e432aade2fb" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">31</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_6630c3118460436bbf1c06d6a34339a9" contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_d0613d6c586e49feab72a616948801dd" contextRef="c20180701to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_bcaabce92e8c4b049a180be9f31b22b7" contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,225</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_160dcfb2e3604ff18da92958b3968a96" contextRef="c20180701to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_622dec14e7144a7eb02667f5a97c5d4d" contextRef="c20180701to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_6c42499de554402280d3775bbcb588e1" contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,226</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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_cece69af14014498bac2170ea2e6bb21" contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_c195541964b64957ab73cf1bb9a796b8" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,226</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: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_e594b0c960034095b7b3afeadd852b0a" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_dd989a94a7a3414f9c8d9c9ccef76384" contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,883</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_90a5d787057f4caf8a9a856ebe4799df" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_7729530f9b3e46f99d9cd96a62e77f46" contextRef="c20180701to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_6fca89d1d55c45c49c8b5fc3cab33865" contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,883</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_73c9bef265c84f2ca25fe41b10ad1848" contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_c43231f29342428cac3c21af502b0587" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,883</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Noncontrolling interest in Akcea Therapeutics, Inc</div></td>
    <td 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: 7%; 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>
    <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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_7db5e110c8f542198fa1a9d98f2559d0" contextRef="c20180701to20180930_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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_a8fbcc1325854db9b27c5f5bf123a6de" contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">22,356</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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_6a8c78038f9746599fc7080366c7863c" contextRef="c20180701to20180930_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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_c990b70a9c6f4f6caed4b0586e87d0f1" contextRef="c20180701to20180930_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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_bf6523db1d824d7f81b4b9893185bcb8" contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">22,356</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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_66c2c13181c74f3598876394d0f48fef" contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">8,413</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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_32db0f97c7cd4f0da0e74967e15dcbe1" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">13,943</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: 20%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at September 30, 2018</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_c3359d08af2e4d5ea198fa0fd127edac" contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,507</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6dde8ef0d2274f8082c6fad9e0e45d69" contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">138</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_ba25a26602644681afcfb523a2e79289" contextRef="c20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,030,313</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6cad5f602ba146659c07b7ce82fd3a23" contextRef="c20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,532</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_79b5bf319fb54532a598cba9b7b244cb" contextRef="c20180930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,287,369</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_ff395584dab641a18e3d808cd3e62b10" contextRef="c20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">710,550</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_f9b7ab5b4a8d4ff1a0501b9ea436e6b1" contextRef="c20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">129,594</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d59c9e81ea9149f7a486f4c99ab791fe" contextRef="c20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">840,144</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; 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: 7%; 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: 7%; 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: 7%; 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: 7%; 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: 7%; 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: 7%; 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: 7%; 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: 7%; 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: 20%; background-color: #FFFFFF;"><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 June 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_c60478aa8c15459f8a7bbd6caa1c8895" contextRef="c20190630_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,393</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_8bfe81137d574448a15e3e272d041aaa" contextRef="c20190630_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_35a91c6a829b43e4aae11e23e41334f5" contextRef="c20190630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,177,222</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_abcd350357194091be5dbe1cd4160111" contextRef="c20190630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">24,252</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_3895fbc3ceaa44dd830723f29b4105b0" contextRef="c20190630_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">883,726</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_29f527152e394382bbffa3e986ef04b8" contextRef="c20190630_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,269,384</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_e29db74b7cef4543bd7e91be4d62c616" contextRef="c20190630_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">187,818</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a891962649e6426d86f6ad7bf0373521" contextRef="c20190630" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,457,202</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_977eba342ad24a3298769cc096cf3e75" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_dd0a32f839f34b2391027fb60a50462e" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_e28dd2aa6b874e569198b6d4d54ef424" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_cfeb877b251a48a7b6cf29adc2f5e57d" contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,163</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_0626ae4513944b6c8712a96434792f82" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,163</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_412fecf833154f7abf690541b132378a" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_c7d8d7c4c5d54ac2ba9ed007b8dd258f" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,163</ix:nonFraction></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: 20%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains (losses), net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_172ac55e7b5a498eb599d2d8f8eec47e" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1867eac944aa41cbae8e3d47abc3d6a7" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_6b57ae9c250e47baa4e97986aadf8c81" contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,110</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_da9d5f151eda4dbcb0bcb75e34a22be4" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_0e0eb1754a8d492691ca654fbbe6eae1" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,110</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_3377027aedf145e2a62b53af92fe76b0" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_854b5b7c73ce47748903f3a041b0888a" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,110</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_29321b0ef52149f9a102167ff8a99b50" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_48560808d032489896d62d1382c76f1e" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_483544f2c05f44ac8b9872662574f3fb" contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_428691c0d8a34530b8ff0a8c41b7850e" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_34958569cbc1462599bcc3ca090dff9b" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_b58932b1827b438fae35d1b25e1d4b74" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_2875fd9f4ab5400dbf518756023a110c" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" 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: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_a026a55810e04bb19308f26ab420ad4d" contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">255</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_39226d96f9604378aed335553da74ceb" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_5f19ce07c41a4e06960e938a80b50a33" contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,130</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_e3b43b28e23c49b8a85c08b6756cf9f0" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_8dfb0d6d1c6e428981aac693f68adbf1" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_da1411573bac461193f714edb592a68a" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,131</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_fdd5b1db910a4419b75154b217f64127" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_8933da663a174dc586e754f61e39c7dc" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,131</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_1b1b261601134ad7b527b00058348fe4" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_69d1f2603695493eb1510e71ac3bbc9b" contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,126</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_951d56bad286435ba8a2246e3e2d423f" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_d21e58738a734502b5f78fb4d2bdef0f" contextRef="c20190701to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_810d53dec70a43e0be887b6141deca77" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,126</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_d9533d71316e44099bc2f2fc6e477a40" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_b9ff5349bf714543a98ce3f88e119830" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,126</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #FFFFFF;"><div style="text-align: left; 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><div style="text-align: left; text-indent: -9pt; margin-left: 9pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span>&#160;</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_5fe714273c30499c9e486064f7b4b5dd" contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">11</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_f79726916e124c468d0230aa19c54f11" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_38c35f2c742f433fb8fa53a4fdef9972" contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,804</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_04539bb1ef754c67ad7a831b15058953" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_6fa83dcbf2634d7eb7d376df35e1b8d3" contextRef="c20190701to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_42df54577138410faaad61b92b513286" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,804</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_dd76df29fa044ea5b2e058e956f56cc5" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2aa42131140c47889666342fdce4bf37" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,804</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Noncontrolling interest in Akcea Therapeutics, Inc.</div></td>
    <td 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: 7%; 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>
    <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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_c86b430bc1b44672ab27e5ef879375cd" contextRef="c20190701to20190930_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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_c237f66e96ba4ce5ab488ab071c5d276" contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,416</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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_2dcfbc0f27804b5787e0e2b93fed5a17" contextRef="c20190701to20190930_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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_d1f78ebc0abe40c0ac4b588df3b79a63" contextRef="c20190701to20190930_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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_94f5913e46be43d18abc42a727c2dc4d" contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,416</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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_65c8e4b39ae34632a51d0bf623f965d0" contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">26,145</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: 7%; 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:MinorityInterestPeriodIncreaseDecrease" id="Fact_ccbca592ee4344dba45e227a44457aab" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,729</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: 20%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at September 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_8fa67994f6bf40e78d066e4f4dc98810" contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,637</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6cf39b5f854044b78edcc8e335e70e92" contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">141</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_55717b5d3d8d40ff8bfe4ffb62adea43" contextRef="c20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,219,090</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_3351e5260ee04c229a9264288b31015a" contextRef="c20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25,375</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_bc6630cc82394fe0aad0e6a861d90412" contextRef="c20190930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">857,563</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_b1d05ec6c8cc4347b88b9e4b4cc010bc" contextRef="c20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,336,293</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_7228c3ff57384f839b30be32c8c414a6" contextRef="c20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">161,673</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_57733ac2866b433db66897b885fa2359" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,497,966</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>6</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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;">Nine Months Ended&#xA0;September 30, 2018 and 2019</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z694ff9091db94c529a6793a02f46a948" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 Ionis</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div></td>
    <td 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;">Noncontrolling</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Interest in Akcea</div></td>
    <td 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; 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;">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>
    <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;">Therapeutics, Inc.</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: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, 2017</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_ddc7cf10a76f451c8b2b4aa0efe7c614" contextRef="c20171231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">124,976</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a3737a74e2c84a07b526c4ecb1d4245c" contextRef="c20171231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">125</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_55211c832be145c1bd2c207a06b16942" contextRef="c20171231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,553,681</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_3dc283c48f254a9e93d024c1485b5603" contextRef="c20171231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">31,759</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_4b1a649e5d604a8c96c1dcb1e3ad86bd" contextRef="c20171231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,241,034</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6cf23cc0d1d5479c83f74cb58288d56d" contextRef="c20171231_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">281,013</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_5c0eaf67f57a4bae8530de2dd3f33960" contextRef="c20171231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">84,267</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a1a91a7e830b48eca3a86d4027d43049" contextRef="c20171231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">365,280</ix:nonFraction></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: 20%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_5ebcb96876e0459bb80e591552daef17" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_aa75c6042a6f439b8c2518d06d3bd5c9" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_67700f9c749f485a924b810c627d5fe2" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_4b2d05bdff834effa429f280a7d40614" contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">46,335</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b3ad397389ef4c399300993e8583e465" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">46,335</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_c202c415a5344cd0b6281508e66a4cc4" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_6f8bfb5eb2c340eda76b9c5c95c0ced0" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">46,335</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains (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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_e62b4a8dd22e492b934e39b29c3d5909" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_e2def5bf3b8443798c0862c0b7342249" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7c0db743213f4c49b2ae444b04c7907b" contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">834</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_b6e9b195dc7940b1b8a4c59f4ef851ed" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_c1cfb7c5586445feaf54b3a96bb62c39" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">834</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_176040219a764acb9fea4deb740d8a91" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_01ca9f1c819e4277af75bc9cef959535" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">834</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: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_1f50a16d37a8423294c83b5ff8b38164" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_982a47fa8d3644dba1e623fb1c2c9476" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_7c2ff3b12307431ebedfab543a17940d" contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">61</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_711f2f613200451fa72ee717ce0bbaaa" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_56f39bd775b844f7a307a9ce09c3c0fd" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">61</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_317f96be510f4c289a8be67492681848" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_330092d5cc7d401e8eba3233459a538a" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">61</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen stock purchase</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesNewIssues" id="Fact_ee0b90d828ff40a3a175772f568db770" contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">11,502</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_7dab409285f142989e81e41b41aaf5cf" contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_a7067d24235942daa663277978ea22ae" contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">447,954</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_1a08a50a788b4034a16580b56c3e38bc" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_e9d67aba016d4976bd285f3e402c73c1" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_ff428e47468f4e02814df9d8a5ada121" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">447,965</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_18b36961e78c489f88760e0d220758f8" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueNewIssues" id="Fact_336ebf4d394a4b42b647d3c11df0a9dc" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">447,965</ix:nonFraction></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: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_d1bdbcaa567441628c2ef5d1031fbf78" contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">1,029</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_be2452b0552b472aa17c5c8ec8461c32" contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_d89629bda2d9446fb6deaafc29258ef4" contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,800</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_097668a314164bd188a8ad54ef3d10b4" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_4a997167d5d94d52b1fe66599f72e392" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_6152078c2e534c709c8a5c523907d682" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,802</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_b7aa80aa648543b7b9b9e3619dd03f2b" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_b9871f32ecc34c30b7eb5dfa2bc8e69b" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,802</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_b598c195eaf84d658146d068c0c83f78" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_431d4cae18b64b6a842b9d25d4549d53" contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">97,210</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_fb9af86803024908a001f5927e85d4b9" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_b3afeeeb5f3d4f898de60e54428d0de8" contextRef="c20180101to20180930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_d4452c91b47547938b176b4e021434fe" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">97,210</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_68a2f0a5e8a04829971f142a38882958" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_d946e571f77b4a4385127d499a8e13ea" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">97,210</ix:nonFraction></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: 20%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Noncontrolling interest in Akcea Therapeutics, Inc</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_c60daf6058434e0fa0e2b6b6bab3b0a9" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_87b2eccc524b4103870bcd8158f0a9a4" contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">83,332</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_09698d9fd4914c40ace49ec141ff6b80" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_f248e268d100429ba20f6264e206af32" contextRef="c20180101to20180930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_3280d89dea3f4bd7ac4b9885cd77c30c" contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">83,332</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_96890ae3e5cf4a06a144890989fe6042" contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">45,327</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_4ede0c53c9634a11bb27f7257027ef80" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">38,005</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at September 30, 2018</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: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_4c7170dee1ec4920a29097e40c6ab19d" contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,507</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_454e18c51da34837a9d7820479c2e2e2" contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">138</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_ab9738c203ec47169572bc2cbda0d754" contextRef="c20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,030,313</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_50080ff24bd94948a26bd1fe84d2aa5b" contextRef="c20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,532</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_fe662f9876344def8011a388c17f60d1" contextRef="c20180930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,287,369</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_5f92ae0c31b94956b30594a52a08f27a" contextRef="c20180930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">710,550</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_c04e5b991c1c40bf831f700f12239cfb" contextRef="c20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">129,594</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_2ed6745c19e8413195da23cac9b05937" contextRef="c20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">840,144</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: 20%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, 2018</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_fee7d7f5efaa4aa1b8c460e4a16ea7fb" contextRef="c20181231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,929</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_4df5adf4881a4a63aec3f101266b76d6" contextRef="c20181231_StatementEquityComponentsAxis_CommonStockMember" 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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_75ec3f39a822463791ea074e335a92f3" contextRef="c20181231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,047,250</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_2029381cbce8449ba45e25f7de96225f" contextRef="c20181231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,016</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_917b2ac712f14901b2e90a6d382fe009" contextRef="c20181231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">967,293</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_9eed7c8ea3e9413dbcaaa1452e62a26b" contextRef="c20181231_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,048,079</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_8424068fab5b4bada989600c1d20bc4f" contextRef="c20181231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">139,081</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_af58a78c084e4e9e8a5ef2a3d3043c47" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,187,160</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_45123936bbd84866b03756a95d0c796d" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_15a72c452d2d43c8a14f170df416dfe3" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_da49e58b5dfb46d6888960e74b977b69" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_6885fdf2ef9441089e89c3277edd2591" contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">109,730</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_d535e4f71bd8461bb45bf7d0ef01492f" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">109,730</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_7225c552985e49a09d45b0ce903f19dd" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_9f847706fda742779fcf3591ba87f390" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">109,730</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized gains (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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_500d46c4bfca4212b740bccf33b982cc" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_e56ff1c2c77d49dda0fe1130a1e01fdd" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_263c693f37e24cb38ed834ecd9a652d1" contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,666</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_376fdc5e2d5b479ea2a236f157d5537c" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_00edfc6f60df4da0b41b16445549a176" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,666</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_be58d9d656da4069ab0f9553b0fae185" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_402e37708d874b35b6711d1421373cf7" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,666</ix:nonFraction></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: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_88d9e3b7bb98403280070f245b2e8b16" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_3947e71e8b954b5c97775df046ed7d5a" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_d3d38dab3b754310b19a7c2ba5a82160" contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_65eae6716a2543ab84ed808dbe813a53" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_61d35598c2c94e1a9c0bf47d40a14425" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_06e96816ce8f44d9b9861ac93493db4b" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_eab7b4251a5547059684440177dbb163" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_bdb084067dec4e639732b2a241b4f0f4" contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,855</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_fc061deeaf414fb385fb62a5657f21ec" contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_9fef205540764632be214acb5b9cec27" contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,132</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_42687c96437b45a39a73ddedbcd192fd" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_16e77799d06342409486a9c092f18725" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_d1952e003b8d42508f6df80dbd78c5d6" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,135</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_b00270a3f4b64871a43c9a22da5d596b" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_8e9cf70e7e0c479ba9e68432d00c69d5" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,135</ix:nonFraction></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: 20%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_9c4912015e674c42beba8d1fc969d3ee" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_7d344d4eb6a14d4792a4b9af3e43a874" contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">111,564</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_79187bc0728d40c9a40cce173e770f10" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_6b5b2407e2f547cbb7e191df8ff07107" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_f8b7027bc5ec4c8f9c7bce7ed24e53fe" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">111,564</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_60c9c72ec2524b40a4692279e84fbf7e" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_a79a3e016e514b4cafe1a09d86429ac5" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">111,564</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;"><div style="text-align: left; 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%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_b1c990bc0d3645be871f64f472db7c23" contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">147</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_9fe5f5ef4d9f4a9cbaf1f12e625fcf6b" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_89d4bdca242243748410d19b1210e6b7" contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,841</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_ef5b034d8f964c1589c910467c9dafec" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_be5b1af1df45469ba696a14d825d9a47" contextRef="c20190101to20190930_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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_4ab66a3a06724a9db9a232bd04e293f3" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,841</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: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_3b4af19eaed34913a08a15ab82011ea5" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_4ed50e4cb7e540b681d94f7ddcd062dd" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,841</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: 20%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Noncontrolling interest in Akcea Therapeutics, Inc.</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_5b3578f4d7a545c28e43ea47e3d4d7e1" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_d1f3c6f6ffce4dcd9171407be72f04d1" contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">33,015</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_4bcf674568a64e19b059ec6ee03afa56" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_26db2a9d491b4ea48759ba7761540a05" contextRef="c20190101to20190930_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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_48a0f306299d4ab7a051da51d2f25d28" contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">33,015</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_9d99df3743a641f29215906163b79924" contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">22,592</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_f26690d213024933b05ccf5cddbe7b1d" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">10,423</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at September 30, 2019</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: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_7cbfdbbb36ca464bae0814eda6c30402" contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,637</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_34f9ec06347a481c849caf2dea53db89" contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">141</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_c5b0fe5c6e0b47fe8cbf429987d130ff" contextRef="c20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,219,090</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_9d0d46e275464c3ebe27d823ecdb52a6" contextRef="c20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25,375</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_7a16ea3be1664c4ba9b0f21232a64560" contextRef="c20190930_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">857,563</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_45103697ee8d4efa8832dff41ebbfa6d" contextRef="c20190930_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,336,293</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_119a87edc2fa4ca8b2bef757fffd3fe2" contextRef="c20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">161,673</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_89506e267f834956b9ee7b9d8fb15786" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,497,966</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;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>7</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z97ddab0179524502bcb04f1dfb4bd73b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; 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 income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: '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:ProfitLoss" id="Fact_f7c36546ee144c2c86ebae7331367498" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99,304</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:ProfitLoss" id="Fact_a21016941dc0429abc056d42872b32b2" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">87,747</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to reconcile net loss to net cash provided by operating activities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </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="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,345</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,650</ix:nonFraction></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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:OperatingLeaseRightOfUseAssetAmortization" id="Fact_9e6711269ac449af9f3ea5cf3d5eaa6a" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,433</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:OperatingLeaseRightOfUseAssetAmortization" id="Fact_5558af291e4642f9823614e737f072ce" contextRef="c20180101to20180930" 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: #FFFFFF; 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="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,139</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,356</ix:nonFraction></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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of premium (discount) on investments, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_246d1c45e9574034a56b56918f85ebb2" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,064</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_4aaed7ae1baf412b9dbc761309827e6d" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">791</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,448</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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="c20180101to20180930" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of convertible senior notes discount</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfDebtDiscountPremium" id="Fact_67a650ffc0ca4c9aae37011987ab83e5" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,747</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfDebtDiscountPremium" id="Fact_b0415b33ed664cbba8c9bfe200890e72" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,781</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_04aaa2990d5a40ad8fdb1b5232b70a08" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">111,564</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_75990e27c7ef4862aef11ff7e8db6961" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">97,210</ix:nonFraction></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%; background-color: #FFFFFF;"><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, licensing and property, plant and equipment</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetImpairmentCharges" id="Fact_7fcd200b638b455db39131034fdc6876" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">216</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetImpairmentCharges" id="Fact_fe5c9b55fb8549bebb24e58da0204a34" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">482</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Provision for deferred income taxes</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_8414c778f38f421ba72eccd5272fd411" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,103</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_21582d84c78941ef9bc300c0128beed5" contextRef="c20180101to20180930" 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: 76%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">33,716</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:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_4adb47def1984cd7bbd6593823908452" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">48,223</ix:nonFraction></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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_6cc57db037e24224babb23341491fa27" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,606</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_855e538885814931adc2c6ca522196ff" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,604</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">23,377</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="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,573</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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_8a994583ad564784b70d134601567caf" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">18,764</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_7d0b289b5d31478faec7c1781df64a2b" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">13,606</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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 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:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_5f5c568dfefd46649d7f965b7bc2f695" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,864</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:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_e29dcd8047ff491884c92796c96013cb" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">892</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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities and deferred rent</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:IncreaseDecreaseInAccruedAndDeferredLiabilities" id="Fact_08f6c9cf45f246f6a33cd0c9749cb737" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,909</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:IncreaseDecreaseInAccruedAndDeferredLiabilities" id="Fact_8da87902979a47b2b8cd9fcda264eef6" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">14,392</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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;">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:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_5d444769c22d417199294bd747e46936" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">97,029</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:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_7536a4e7a5c548658c9c6c4190e7e76b" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">447,168</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; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by operating activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_66c31f18a56f439ab964f9bf11cd801d" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">67,788</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_aaaa638d546d45448755c94c63222ccd" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">487,398</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Purchases 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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_083200534ca3433a9d3c58296e5b5402" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,617,726</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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_50e0b935822448d399c6da50df573ca5" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,156,335</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from short-term investments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_421423d1ea9a4d73aef63e7e59de4afb" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,465,600</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_6dc4fafd64864e3188177206b20e21e5" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">568,517</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;">Purchases of property, plant and equipment</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_5c4c86b4988a4bcc93f568312cf27532" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">23,143</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:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_23746708bcf2482183689f1b17ed01be" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,221</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:PaymentsToAcquireLicensesAndOtherAssets" id="Fact_bedfe0d50deb453aac9adee6a16b847b" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,196</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:PaymentsToAcquireLicensesAndOtherAssets" id="Fact_2503d109e9bf429abba6e180534abb50" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,317</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </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 investing activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_92cb4d2048d14989a03cc74060fe995e" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">179,465</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:NetCashProvidedByUsedInInvestingActivities" id="Fact_98c358a7d9cc4f7dbda064764db082d3" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">603,356</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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_ddb0c2b46432418f9be1b92d0e804ae9" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,137</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_8bffc0bd215e4f839416df4a6531312e" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,254</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 17.85pt; 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</div><div style="text-align: left; text-indent: 17.85pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">employee stock options</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b75a3de029544b8ea1fafba1be80eb98" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,841</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:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2013b605a8914f73b56ab03781e33c14" contextRef="c20180101to20180930" 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: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from the issuance of common stock to Biogen</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_debd829012124436b0de04a28fa90961" contextRef="c20190101to20190930" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_54f753502f1e48f180c1bc730693f37d" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">447,965</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;">Principal payments on debt obligations</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:RepaymentsOfLongTermDebt" id="Fact_879a061318dd4c3eb2790021bc1151c3" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,500</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:RepaymentsOfLongTermDebt" id="Fact_c0b4ad7116ba4f3db97cd83f155e9a38" contextRef="c20180101to20180930" 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; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by financing activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_eaaca3e288be4952adf9a7f8f7bf8f92" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">80,796</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInFinancingActivities" id="Fact_af5d9d765265424f939925e68f5a2822" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">466,219</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net increase in cash and cash equivalents</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" id="Fact_d3528cb59540483eab0bc9587f782713" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">30,881</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" id="Fact_6c7116234ecd426ba14d70e6a235d6d3" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">350,261</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;">Cash and cash equivalents at beginning of period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_fd5df9e35af74f35a9bce6f143774041" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">278,820</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_23118be8b83a46f58f22e69cb8f9077f" contextRef="c20171231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">129,630</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_501d02ebc89a4528bbf4865fc32ff7e1" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">247,939</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_ca87839d08a24d358e12b10cb090aa04" contextRef="c20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">479,891</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Interest 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:InterestPaidNet" id="Fact_9c49e11cb9ce4f04aa4b433d927debc7" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,474</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_fa5b8cf53b3c4bf1895fa0b855713236" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,434</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes paid</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaid" id="Fact_7cebb5b6555248abbae68e2f9f007feb" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,037</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaid" id="Fact_aefef64320704192be3ed39022abf12f" contextRef="c20180101to20180930" 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: #FFFFFF; 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%; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Right-of-use assets obtained in exchange for lease 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;"><div style="font-family: '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:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_e6053bdbbbff4c51841678e272ea95e7" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,178</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_d8be1f56d6d14b7d84ffa49e06d25230" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts accrued for capital and patent expenditures</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:NonCashCapitalAndPatentExpenditures" id="Fact_dacc7af35ad249f79558b3fe83347b6a" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,251</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:NonCashCapitalAndPatentExpenditures" id="Fact_85c1067a8a3d410db856b7d9c92b35c6" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,296</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of property, plant and equipment included in long-term obligations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:CapitalExpendituresIncurredButNotYetPaid" id="Fact_1dd1fdaf707e40b694575f1bfaa77147" contextRef="c20190101to20190930" 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:CapitalExpendituresIncurredButNotYetPaid" id="Fact_9ae6012fd0b94c25a1d0a9e5f51de08d" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,596</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><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;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>8</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">September 30, 2019</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_b498b17d23e34d2589e5773394842304" contextRef="c20190101to20190930" escape="true" continuedAt="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d1">
<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_8fa2f2f841bf48e8aebe2e12cdb0c52d1" continuedAt="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d2">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d2" continuedAt="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d3"><ix:nonNumeric name="us-gaap:BasisOfAccountingPolicyPolicyTextBlock" id="Text_905a4e511c60423b989b43e99337abf6" contextRef="c20190101to20190930" 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 and nine months ended&#xA0;September 30, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 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_8fa2f2f841bf48e8aebe2e12cdb0c52d3" continuedAt="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d4">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d4" continuedAt="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d5"><ix:nonNumeric name="us-gaap:ConsolidationPolicyTextBlock" id="Text_c4fe943e7ede4d098552ec8bdd246050" contextRef="c20190101to20190930" 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;">In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. </span>In July 2017, Akcea completed an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO,</span> and therefore, beginning in July 2017, we no longer owned <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_5363570e60de48029520ca50e5d8bcc6" contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent of Akcea. In the first quarter of 2019, we received <ix:nonFraction name="ions:ReceiptOfSharesInSubsidiary" id="Fact_7d73810a223b46b69a6b2753b0deaba8" contextRef="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6">2.8</ix:nonFraction> million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx.</sub>. At September 30, 2019, our ownership was approximately <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_41aca5c969014ccb8a724b491c9c534a" contextRef="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">75</ix:nonFraction> percent. In the fourth quarter of 2019, we expect to receive an additional <ix:nonFraction name="ions:ReceiptOfSharesInSubsidiary" id="Fact_8ae685fa3c5b421b95d53e7fe1b68c91" contextRef="c20191001to20191231_OwnershipAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.9</ix:nonFraction> million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx</sub>. We reflect changes in our ownership of Akcea in our financial statements in the period the change occurs. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled &#8220;Noncontrolling Interest in Akcea&#8221; in Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies,</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further information related to our accounting for our investment in Akcea.</span></div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d5" continuedAt="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_8fa2f2f841bf48e8aebe2e12cdb0c52d6">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unless the context requires otherwise, &#8220;Ionis&#8221;, &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and its majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries.</div>
</ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:SignificantAccountingPoliciesTextBlock" id="Text_e79356058bb74d2aa7d3df4a10cdfef1" contextRef="c20190101to20190930" escape="true" continuedAt="Text_857e0866feaf4794bd379968f87519771">
<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_857e0866feaf4794bd379968f87519771" continuedAt="Text_857e0866feaf4794bd379968f87519772">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:RevenueFromContractWithCustomerPolicyTextBlock" id="Text_a7941b74efeb4884837e75cd6f25191b" contextRef="c20190101to20190930" escape="true" continuedAt="Text_34918020276946e4a34cbeb1b243c4711"><ix:continuation id="Text_857e0866feaf4794bd379968f87519772" continuedAt="Text_857e0866feaf4794bd379968f87519773">
<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="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</span></div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4711" continuedAt="Text_34918020276946e4a34cbeb1b243c4712"><ix:continuation id="Text_857e0866feaf4794bd379968f87519773" continuedAt="Text_857e0866feaf4794bd379968f87519774">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4712" continuedAt="Text_34918020276946e4a34cbeb1b243c4713"><ix:continuation id="Text_857e0866feaf4794bd379968f87519774" continuedAt="Text_857e0866feaf4794bd379968f87519775">
<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;"><span style="text-decoration: underline;">Our Revenue Sources</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4713" continuedAt="Text_34918020276946e4a34cbeb1b243c4714"><ix:continuation id="Text_857e0866feaf4794bd379968f87519775" continuedAt="Text_857e0866feaf4794bd379968f87519776">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4714" continuedAt="Text_34918020276946e4a34cbeb1b243c4715"><ix:continuation id="Text_857e0866feaf4794bd379968f87519776" continuedAt="Text_857e0866feaf4794bd379968f87519777">
<div 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 consolidated balance sheet.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4715" continuedAt="Text_34918020276946e4a34cbeb1b243c4716"><ix:continuation id="Text_857e0866feaf4794bd379968f87519777" continuedAt="Text_857e0866feaf4794bd379968f87519778">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4716" continuedAt="Text_34918020276946e4a34cbeb1b243c4717"><ix:continuation id="Text_857e0866feaf4794bd379968f87519778" continuedAt="Text_857e0866feaf4794bd379968f87519779">
<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_34918020276946e4a34cbeb1b243c4717" continuedAt="Text_34918020276946e4a34cbeb1b243c4718"><ix:continuation id="Text_857e0866feaf4794bd379968f87519779" continuedAt="Text_857e0866feaf4794bd379968f875197710">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4718" continuedAt="Text_34918020276946e4a34cbeb1b243c4719"><ix:continuation id="Text_857e0866feaf4794bd379968f875197710" continuedAt="Text_857e0866feaf4794bd379968f875197711">
<div 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 future sales milestone payments and royalties we earn under our partnerships.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c4719" continuedAt="Text_34918020276946e4a34cbeb1b243c47110"><ix:continuation id="Text_857e0866feaf4794bd379968f875197711" continuedAt="Text_857e0866feaf4794bd379968f875197712">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47110" continuedAt="Text_34918020276946e4a34cbeb1b243c47111"><ix:continuation id="Text_857e0866feaf4794bd379968f875197712" continuedAt="Text_857e0866feaf4794bd379968f875197713">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: Product sales, net</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47111" continuedAt="Text_34918020276946e4a34cbeb1b243c47112"><ix:continuation id="Text_857e0866feaf4794bd379968f875197713" continuedAt="Text_857e0866feaf4794bd379968f875197714">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47112" continuedAt="Text_34918020276946e4a34cbeb1b243c47113"><ix:continuation id="Text_857e0866feaf4794bd379968f875197714" continuedAt="Text_857e0866feaf4794bd379968f875197715">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. </span>In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Europe, prior to the third quarter of 2019 we distributed TEGSEDI through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL was our sole customer in Europe. The 3PL in Europe then distributed TEGSEDI to hospitals and pharmacies. In the third quarter of 2019, we entered into a distribution arrangement with a 3PL and began to sell both TEGSEDI and WAYLIVRA directly to hospitals and pharmacies in Europe.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47113" continuedAt="Text_34918020276946e4a34cbeb1b243c47114"><ix:continuation id="Text_857e0866feaf4794bd379968f875197715" continuedAt="Text_857e0866feaf4794bd379968f875197716">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47114" continuedAt="Text_34918020276946e4a34cbeb1b243c47115"><ix:continuation id="Text_857e0866feaf4794bd379968f875197716" continuedAt="Text_857e0866feaf4794bd379968f875197717">
<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_34918020276946e4a34cbeb1b243c47115" continuedAt="Text_34918020276946e4a34cbeb1b243c47116"><ix:continuation id="Text_857e0866feaf4794bd379968f875197717" continuedAt="Text_857e0866feaf4794bd379968f875197718">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47116" continuedAt="Text_34918020276946e4a34cbeb1b243c47117"><ix:continuation id="Text_857e0866feaf4794bd379968f875197718" continuedAt="Text_857e0866feaf4794bd379968f875197719">
<div 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_34918020276946e4a34cbeb1b243c47117" continuedAt="Text_34918020276946e4a34cbeb1b243c47118"><ix:continuation id="Text_857e0866feaf4794bd379968f875197719" continuedAt="Text_857e0866feaf4794bd379968f875197720">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47118" continuedAt="Text_34918020276946e4a34cbeb1b243c47119"><ix:continuation id="Text_857e0866feaf4794bd379968f875197720" continuedAt="Text_857e0866feaf4794bd379968f875197721">
<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 provide details about our collaboration agreements in Note 7, </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;"> in our Annual Report on Form 10-K for the year ended December 31, 2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47119" continuedAt="Text_34918020276946e4a34cbeb1b243c47120"><ix:continuation id="Text_857e0866feaf4794bd379968f875197721" continuedAt="Text_857e0866feaf4794bd379968f875197722">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>9</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47120" continuedAt="Text_34918020276946e4a34cbeb1b243c47121"><ix:continuation id="Text_857e0866feaf4794bd379968f875197722" continuedAt="Text_857e0866feaf4794bd379968f875197723">
<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;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47121" continuedAt="Text_34918020276946e4a34cbeb1b243c47122"><ix:continuation id="Text_857e0866feaf4794bd379968f875197723" continuedAt="Text_857e0866feaf4794bd379968f875197724">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47122" continuedAt="Text_34918020276946e4a34cbeb1b243c47123"><ix:continuation id="Text_857e0866feaf4794bd379968f875197724" continuedAt="Text_857e0866feaf4794bd379968f875197725">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47123" continuedAt="Text_34918020276946e4a34cbeb1b243c47124"><ix:continuation id="Text_857e0866feaf4794bd379968f875197725" continuedAt="Text_857e0866feaf4794bd379968f875197726">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197726" continuedAt="Text_857e0866feaf4794bd379968f875197727"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47124" continuedAt="Text_34918020276946e4a34cbeb1b243c47125">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za828ef045c5342ec950720727f58194e">
  <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></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47125" continuedAt="Text_34918020276946e4a34cbeb1b243c47126"><ix:continuation id="Text_857e0866feaf4794bd379968f875197727" continuedAt="Text_857e0866feaf4794bd379968f875197728">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47126" continuedAt="Text_34918020276946e4a34cbeb1b243c47127"><ix:continuation id="Text_857e0866feaf4794bd379968f875197728" continuedAt="Text_857e0866feaf4794bd379968f875197729">
<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_34918020276946e4a34cbeb1b243c47127" continuedAt="Text_34918020276946e4a34cbeb1b243c47128"><ix:continuation id="Text_857e0866feaf4794bd379968f875197729" continuedAt="Text_857e0866feaf4794bd379968f875197730">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197730" continuedAt="Text_857e0866feaf4794bd379968f875197731"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47128" continuedAt="Text_34918020276946e4a34cbeb1b243c47129">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z423ff748c87641c8b173de2f4fc02db9">
  <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></div>
</div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197731" continuedAt="Text_857e0866feaf4794bd379968f875197732"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47129" continuedAt="Text_34918020276946e4a34cbeb1b243c47130">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zf1c5606cc4d545ceaeee39b9216b6706">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197732" continuedAt="Text_857e0866feaf4794bd379968f875197733"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47130" continuedAt="Text_34918020276946e4a34cbeb1b243c47131">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd1b38b04c6d44ee2a317b490bdd9a611">
  <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></div>
</div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197733" continuedAt="Text_857e0866feaf4794bd379968f875197734"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47131" continuedAt="Text_34918020276946e4a34cbeb1b243c47132">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zdc1a47e8a7f84ce9b17a88c78aaa2813">
  <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 is probable. </div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47132" continuedAt="Text_34918020276946e4a34cbeb1b243c47133"><ix:continuation id="Text_857e0866feaf4794bd379968f875197734" continuedAt="Text_857e0866feaf4794bd379968f875197735">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197735" continuedAt="Text_857e0866feaf4794bd379968f875197736"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47133" continuedAt="Text_34918020276946e4a34cbeb1b243c47134">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z154b7c49dc104a57ab977ae0e4e30809">
  <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;">2.</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></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47134" continuedAt="Text_34918020276946e4a34cbeb1b243c47135"><ix:continuation id="Text_857e0866feaf4794bd379968f875197736" continuedAt="Text_857e0866feaf4794bd379968f875197737">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47135" continuedAt="Text_34918020276946e4a34cbeb1b243c47136"><ix:continuation id="Text_857e0866feaf4794bd379968f875197737" continuedAt="Text_857e0866feaf4794bd379968f875197738">
<div 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 the distinct goods and services we are required to provide under the contract. Accounting rules refer to these as our performance obligations. We typically have only <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" id="Fact_a5d99bad3ce4453ea2bcc34d06e92ad6" contextRef="c20190101to20190930" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation at the inception of a contract, which is to perform R&amp;D services.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47136" continuedAt="Text_34918020276946e4a34cbeb1b243c47137"><ix:continuation id="Text_857e0866feaf4794bd379968f875197738" continuedAt="Text_857e0866feaf4794bd379968f875197739">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47137" continuedAt="Text_34918020276946e4a34cbeb1b243c47138"><ix:continuation id="Text_857e0866feaf4794bd379968f875197739" continuedAt="Text_857e0866feaf4794bd379968f875197740">
<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 times 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. These items are contingent upon future events that may not occur. 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_34918020276946e4a34cbeb1b243c47138" continuedAt="Text_34918020276946e4a34cbeb1b243c47139"><ix:continuation id="Text_857e0866feaf4794bd379968f875197740" continuedAt="Text_857e0866feaf4794bd379968f875197741">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47139" continuedAt="Text_34918020276946e4a34cbeb1b243c47140"><ix:continuation id="Text_857e0866feaf4794bd379968f875197741" continuedAt="Text_857e0866feaf4794bd379968f875197742">
<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_34918020276946e4a34cbeb1b243c47140" continuedAt="Text_34918020276946e4a34cbeb1b243c47141"><ix:continuation id="Text_857e0866feaf4794bd379968f875197742" continuedAt="Text_857e0866feaf4794bd379968f875197743">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197743" continuedAt="Text_857e0866feaf4794bd379968f875197744"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47141" continuedAt="Text_34918020276946e4a34cbeb1b243c47142">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0c7f5c3635d344b3a58160ef8667cdcd">
  <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></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47142" continuedAt="Text_34918020276946e4a34cbeb1b243c47143"><ix:continuation id="Text_857e0866feaf4794bd379968f875197744" continuedAt="Text_857e0866feaf4794bd379968f875197745">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47143" continuedAt="Text_34918020276946e4a34cbeb1b243c47144"><ix:continuation id="Text_857e0866feaf4794bd379968f875197745" continuedAt="Text_857e0866feaf4794bd379968f875197746">
<div 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 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><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47144" continuedAt="Text_34918020276946e4a34cbeb1b243c47145"><ix:continuation id="Text_857e0866feaf4794bd379968f875197746" continuedAt="Text_857e0866feaf4794bd379968f875197747">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47145" continuedAt="Text_34918020276946e4a34cbeb1b243c47146"><ix:continuation id="Text_857e0866feaf4794bd379968f875197747" continuedAt="Text_857e0866feaf4794bd379968f875197748">
<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 are usually based on scientific progress. For example, in the first quarter of 2019, we earned $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_df927636533f42d0b09abafe0eac07cb" contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million in milestone payments from Roche when Roche dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx </sub>(RG6042). We did not consider these milestone payments probable until Roche achieved the milestone event because the dosing of a patient was a contingent event that was not within our control. We recognized the milestone payments in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payments.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47146" continuedAt="Text_34918020276946e4a34cbeb1b243c47147"><ix:continuation id="Text_857e0866feaf4794bd379968f875197748" continuedAt="Text_857e0866feaf4794bd379968f875197749">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197749" continuedAt="Text_857e0866feaf4794bd379968f875197750"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47147" continuedAt="Text_34918020276946e4a34cbeb1b243c47148">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z6b0a5e16e14f413e9cb3790671d564a2">
  <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: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47148" continuedAt="Text_34918020276946e4a34cbeb1b243c47149"><ix:continuation id="Text_857e0866feaf4794bd379968f875197750" continuedAt="Text_857e0866feaf4794bd379968f875197751">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47149" continuedAt="Text_34918020276946e4a34cbeb1b243c47150"><ix:continuation id="Text_857e0866feaf4794bd379968f875197751" continuedAt="Text_857e0866feaf4794bd379968f875197752">
<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.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47150" continuedAt="Text_34918020276946e4a34cbeb1b243c47151"><ix:continuation id="Text_857e0866feaf4794bd379968f875197752" continuedAt="Text_857e0866feaf4794bd379968f875197753">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>10</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47151" continuedAt="Text_34918020276946e4a34cbeb1b243c47152"><ix:continuation id="Text_857e0866feaf4794bd379968f875197753" continuedAt="Text_857e0866feaf4794bd379968f875197754">
<div 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_34918020276946e4a34cbeb1b243c47152" continuedAt="Text_34918020276946e4a34cbeb1b243c47153"><ix:continuation id="Text_857e0866feaf4794bd379968f875197754" continuedAt="Text_857e0866feaf4794bd379968f875197755">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197755" continuedAt="Text_857e0866feaf4794bd379968f875197756"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47153" continuedAt="Text_34918020276946e4a34cbeb1b243c47154">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z1050d76f512c44499a8a4a55c6cd90ec">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197756" continuedAt="Text_857e0866feaf4794bd379968f875197757"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47154" continuedAt="Text_34918020276946e4a34cbeb1b243c47155">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc0968e72382e45d9a26ab5eae98b5ed7">
  <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 on future product sales;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197757" continuedAt="Text_857e0866feaf4794bd379968f875197758"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47155" continuedAt="Text_34918020276946e4a34cbeb1b243c47156">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zdc34827c6d5d41dabfa0b3a3713d80db">
  <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;">Contractual milestone payments;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197758" continuedAt="Text_857e0866feaf4794bd379968f875197759"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47156" continuedAt="Text_34918020276946e4a34cbeb1b243c47157">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc92b502b421a42638f6c4797795c4af4">
  <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;">Expenses we expect to incur;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197759" continuedAt="Text_857e0866feaf4794bd379968f875197760"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47157" continuedAt="Text_34918020276946e4a34cbeb1b243c47158">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc9eaca6cecc84fc5a8f56282da85c4c1">
  <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;">Income taxes; and</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197760" continuedAt="Text_857e0866feaf4794bd379968f875197761"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47158" continuedAt="Text_34918020276946e4a34cbeb1b243c47159">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9f345c6a9ccf4de79419b350e5a3fc46">
  <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></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47159" continuedAt="Text_34918020276946e4a34cbeb1b243c47160"><ix:continuation id="Text_857e0866feaf4794bd379968f875197761" continuedAt="Text_857e0866feaf4794bd379968f875197762">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47160" continuedAt="Text_34918020276946e4a34cbeb1b243c47161"><ix:continuation id="Text_857e0866feaf4794bd379968f875197762" continuedAt="Text_857e0866feaf4794bd379968f875197763">
<div 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_34918020276946e4a34cbeb1b243c47161" continuedAt="Text_34918020276946e4a34cbeb1b243c47162"><ix:continuation id="Text_857e0866feaf4794bd379968f875197763" continuedAt="Text_857e0866feaf4794bd379968f875197764">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197764" continuedAt="Text_857e0866feaf4794bd379968f875197765"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47162" continuedAt="Text_34918020276946e4a34cbeb1b243c47163">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z7a4859a1235b498a8927bb7e99a59f30">
  <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 number of internal hours we estimate we will spend performing these services;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197765" continuedAt="Text_857e0866feaf4794bd379968f875197766"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47163" continuedAt="Text_34918020276946e4a34cbeb1b243c47164">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z479e033d5771475ab32e613cf9bf9239">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197766" continuedAt="Text_857e0866feaf4794bd379968f875197767"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47164" continuedAt="Text_34918020276946e4a34cbeb1b243c47165">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z781255f68a404a85aa0ec8ffb0f8d24f">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197767" continuedAt="Text_857e0866feaf4794bd379968f875197768"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47165" continuedAt="Text_34918020276946e4a34cbeb1b243c47166">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z6ce136f034fc4177890b3f2eae4d4f3a">
  <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></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47166" continuedAt="Text_34918020276946e4a34cbeb1b243c47167"><ix:continuation id="Text_857e0866feaf4794bd379968f875197768" continuedAt="Text_857e0866feaf4794bd379968f875197769">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47167" continuedAt="Text_34918020276946e4a34cbeb1b243c47168"><ix:continuation id="Text_857e0866feaf4794bd379968f875197769" continuedAt="Text_857e0866feaf4794bd379968f875197770">
<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_34918020276946e4a34cbeb1b243c47168" continuedAt="Text_34918020276946e4a34cbeb1b243c47169"><ix:continuation id="Text_857e0866feaf4794bd379968f875197770" continuedAt="Text_857e0866feaf4794bd379968f875197771">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47169" continuedAt="Text_34918020276946e4a34cbeb1b243c47170"><ix:continuation id="Text_857e0866feaf4794bd379968f875197771" continuedAt="Text_857e0866feaf4794bd379968f875197772">
<div 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 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_34918020276946e4a34cbeb1b243c47170" continuedAt="Text_34918020276946e4a34cbeb1b243c47171"><ix:continuation id="Text_857e0866feaf4794bd379968f875197772" continuedAt="Text_857e0866feaf4794bd379968f875197773">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f875197773" continuedAt="Text_857e0866feaf4794bd379968f875197774"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47171" continuedAt="Text_34918020276946e4a34cbeb1b243c47172">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb5abc673cc6d48aa89e5180f190cfad5">
  <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></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47172" continuedAt="Text_34918020276946e4a34cbeb1b243c47173"><ix:continuation id="Text_857e0866feaf4794bd379968f875197774" continuedAt="Text_857e0866feaf4794bd379968f875197775">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -54pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47173" continuedAt="Text_34918020276946e4a34cbeb1b243c47174"><ix:continuation id="Text_857e0866feaf4794bd379968f875197775" continuedAt="Text_857e0866feaf4794bd379968f875197776">
<div 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_34918020276946e4a34cbeb1b243c47174" continuedAt="Text_34918020276946e4a34cbeb1b243c47175"><ix:continuation id="Text_857e0866feaf4794bd379968f875197776" continuedAt="Text_857e0866feaf4794bd379968f875197777">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47175" continuedAt="Text_34918020276946e4a34cbeb1b243c47176"><ix:continuation id="Text_857e0866feaf4794bd379968f875197777" continuedAt="Text_857e0866feaf4794bd379968f875197778">
<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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. For example, </span>in the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation under our<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2013 Strategic Neurology collaboration with Biogen</span>. As of September 30, 2019, we have completed a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> significant portion of the research and development services. We expect to complete the remainder of our services in 2020. As a result of our change in estimate, in the third quarter of 2019, we recorded a cumulative catch up adjustment of $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_517d03b46cca46a9b5decb28e94b3566" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">16.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to decrease revenue. We expect to complete the remainder of our services in 2020. Refer to Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further discussion of the cumulative catch up adjustment we made.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47176" continuedAt="Text_34918020276946e4a34cbeb1b243c47177"><ix:continuation id="Text_857e0866feaf4794bd379968f875197778" continuedAt="Text_857e0866feaf4794bd379968f875197779">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47177" continuedAt="Text_34918020276946e4a34cbeb1b243c47178"><ix:continuation id="Text_857e0866feaf4794bd379968f875197779" continuedAt="Text_857e0866feaf4794bd379968f875197780">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47178" continuedAt="Text_34918020276946e4a34cbeb1b243c47179"><ix:continuation id="Text_857e0866feaf4794bd379968f875197780" continuedAt="Text_857e0866feaf4794bd379968f875197781">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47179" continuedAt="Text_34918020276946e4a34cbeb1b243c47180"><ix:continuation id="Text_857e0866feaf4794bd379968f875197781" continuedAt="Text_857e0866feaf4794bd379968f875197782">
<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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47180" continuedAt="Text_34918020276946e4a34cbeb1b243c47181"><ix:continuation id="Text_857e0866feaf4794bd379968f875197782" continuedAt="Text_857e0866feaf4794bd379968f875197783">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47181" continuedAt="Text_34918020276946e4a34cbeb1b243c47182"><ix:continuation id="Text_857e0866feaf4794bd379968f875197783" continuedAt="Text_857e0866feaf4794bd379968f875197784">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue in the period in which the counterparty sells the related product, which in certain cases may require us to estimate our royalty revenue. </span>We recognize royalties from SPINRAZA sales in the period in which Biogen records the sale of SPINRAZA.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47182" continuedAt="Text_34918020276946e4a34cbeb1b243c47183"><ix:continuation id="Text_857e0866feaf4794bd379968f875197784" continuedAt="Text_857e0866feaf4794bd379968f875197785">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47183" continuedAt="Text_34918020276946e4a34cbeb1b243c47184"><ix:continuation id="Text_857e0866feaf4794bd379968f875197785" continuedAt="Text_857e0866feaf4794bd379968f875197786">
<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;"><span style="text-decoration: underline;">Commercial Revenue: Product sales, net</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47184" continuedAt="Text_34918020276946e4a34cbeb1b243c47185"><ix:continuation id="Text_857e0866feaf4794bd379968f875197786" continuedAt="Text_857e0866feaf4794bd379968f875197787">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47185" continuedAt="Text_34918020276946e4a34cbeb1b243c47186"><ix:continuation id="Text_857e0866feaf4794bd379968f875197787" continuedAt="Text_857e0866feaf4794bd379968f875197788">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize product sales in the period </span>when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47186" continuedAt="Text_34918020276946e4a34cbeb1b243c47187"><ix:continuation id="Text_857e0866feaf4794bd379968f875197788" continuedAt="Text_857e0866feaf4794bd379968f875197789">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>11</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47187" continuedAt="Text_34918020276946e4a34cbeb1b243c47188"><ix:continuation id="Text_857e0866feaf4794bd379968f875197789" continuedAt="Text_857e0866feaf4794bd379968f875197790">
<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 Product sales</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47188" continuedAt="Text_34918020276946e4a34cbeb1b243c47189"><ix:continuation id="Text_857e0866feaf4794bd379968f875197790" continuedAt="Text_857e0866feaf4794bd379968f875197791">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47189" continuedAt="Text_34918020276946e4a34cbeb1b243c47190"><ix:continuation id="Text_857e0866feaf4794bd379968f875197791" continuedAt="Text_857e0866feaf4794bd379968f875197792">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47190" continuedAt="Text_34918020276946e4a34cbeb1b243c47191"><ix:continuation id="Text_857e0866feaf4794bd379968f875197792" continuedAt="Text_857e0866feaf4794bd379968f875197793">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47191" continuedAt="Text_34918020276946e4a34cbeb1b243c47192"><ix:continuation id="Text_857e0866feaf4794bd379968f875197793" continuedAt="Text_857e0866feaf4794bd379968f875197794">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are the components of variable consideration related to product sales:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47192" continuedAt="Text_34918020276946e4a34cbeb1b243c47193"><ix:continuation id="Text_857e0866feaf4794bd379968f875197794" continuedAt="Text_857e0866feaf4794bd379968f875197795">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47193" continuedAt="Text_34918020276946e4a34cbeb1b243c47194"><ix:continuation id="Text_857e0866feaf4794bd379968f875197795" continuedAt="Text_857e0866feaf4794bd379968f875197796">
<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Chargebacks: </span>In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record reserves for these chargebacks related to product sales to our U.S. customer during the reporting period.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f875197796" continuedAt="Text_857e0866feaf4794bd379968f875197797"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47194" continuedAt="Text_34918020276946e4a34cbeb1b243c47195">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47195" continuedAt="Text_34918020276946e4a34cbeb1b243c47196"><ix:continuation id="Text_857e0866feaf4794bd379968f875197797" continuedAt="Text_857e0866feaf4794bd379968f875197798">
<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Government rebates</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">: We are subject t</span>o discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47196" continuedAt="Text_34918020276946e4a34cbeb1b243c47197"><ix:continuation id="Text_857e0866feaf4794bd379968f875197798" continuedAt="Text_857e0866feaf4794bd379968f875197799">
<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47197" continuedAt="Text_34918020276946e4a34cbeb1b243c47198"><ix:continuation id="Text_857e0866feaf4794bd379968f875197799" continuedAt="Text_857e0866feaf4794bd379968f8751977100">
<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Trade discounts: </span>We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977100" continuedAt="Text_857e0866feaf4794bd379968f8751977101"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47198" continuedAt="Text_34918020276946e4a34cbeb1b243c47199">
<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977101" continuedAt="Text_857e0866feaf4794bd379968f8751977102"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c47199" continuedAt="Text_34918020276946e4a34cbeb1b243c471100">
<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Distribution services</span>: We receive and pay for various distribution services from our U.S. and EU customers and wholesalers in the U.S. For services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value, we classify the costs for such services as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as selling, general and administration, or SG&amp;A, expenses.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471100" continuedAt="Text_34918020276946e4a34cbeb1b243c471101"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977102" continuedAt="Text_857e0866feaf4794bd379968f8751977103">
<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471101" continuedAt="Text_34918020276946e4a34cbeb1b243c471102"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977103" continuedAt="Text_857e0866feaf4794bd379968f8751977104">
<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Product returns: </span>Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#8217;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we believe we will have minimal returns. Our EU customers only take title to the product after they receive an order from a hospital or pharmacy and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in the EU and we do not estimate returns in the EU.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471102" continuedAt="Text_34918020276946e4a34cbeb1b243c471103"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977104" continuedAt="Text_857e0866feaf4794bd379968f8751977105">
<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471103" continuedAt="Text_34918020276946e4a34cbeb1b243c471104"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977105" continuedAt="Text_857e0866feaf4794bd379968f8751977106">
<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Other incentives: </span>In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471104" continuedAt="Text_34918020276946e4a34cbeb1b243c471105"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977106" continuedAt="Text_857e0866feaf4794bd379968f8751977107">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>12</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471105" continuedAt="Text_34918020276946e4a34cbeb1b243c471106"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977107" continuedAt="Text_857e0866feaf4794bd379968f8751977108">
<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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471106" continuedAt="Text_34918020276946e4a34cbeb1b243c471107"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977108" continuedAt="Text_857e0866feaf4794bd379968f8751977109">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471107" continuedAt="Text_34918020276946e4a34cbeb1b243c471108"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977109" continuedAt="Text_857e0866feaf4794bd379968f8751977110">
<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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Upfront payments</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471108" continuedAt="Text_34918020276946e4a34cbeb1b243c471109"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977110" continuedAt="Text_857e0866feaf4794bd379968f8751977111">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471109" continuedAt="Text_34918020276946e4a34cbeb1b243c471110"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977111" continuedAt="Text_857e0866feaf4794bd379968f8751977112">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases</span>, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_72588160d9344e3d91319fe6a66f7d24" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&amp;D services. We are amortizing the $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df2e1cb511f24d2a84b6cc2d7d4dc617" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471110" continuedAt="Text_34918020276946e4a34cbeb1b243c471111"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977112" continuedAt="Text_857e0866feaf4794bd379968f8751977113">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471111" continuedAt="Text_34918020276946e4a34cbeb1b243c471112"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977113" continuedAt="Text_857e0866feaf4794bd379968f8751977114">
<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;"><span style="text-decoration: underline;">Milestone payments</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471112" continuedAt="Text_34918020276946e4a34cbeb1b243c471113"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977114" continuedAt="Text_857e0866feaf4794bd379968f8751977115">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471113" continuedAt="Text_34918020276946e4a34cbeb1b243c471114"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977115" continuedAt="Text_857e0866feaf4794bd379968f8751977116">
<div 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 there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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_34918020276946e4a34cbeb1b243c471114" continuedAt="Text_34918020276946e4a34cbeb1b243c471115"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977116" continuedAt="Text_857e0866feaf4794bd379968f8751977117">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471115" continuedAt="Text_34918020276946e4a34cbeb1b243c471116"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977117" continuedAt="Text_857e0866feaf4794bd379968f8751977118">
<div 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 second quarter of 2019, we achieved a $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPriceAdditions" id="Fact_b1ad7b69ba7b4f49953ac99ff42d86a8" contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million milestone payment from Biogen when we advanced a new target for an unidentified neurological disease under our 2018 strategic neurology 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_34918020276946e4a34cbeb1b243c471116" continuedAt="Text_34918020276946e4a34cbeb1b243c471117"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977118" continuedAt="Text_857e0866feaf4794bd379968f8751977119">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471117" continuedAt="Text_34918020276946e4a34cbeb1b243c471118"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977119" continuedAt="Text_857e0866feaf4794bd379968f8751977120">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2019, we recognized an $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f61ab49d136d4efaa1f8b5c47333b449" contextRef="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">8</ix:nonFraction> million milestone payment <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">when Biogen initiated a Phase 1/2 study of IONIS-LRRK2</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (BIIB094) for the treatment of people with Parkinson&#8217;s disease</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payment was not related to our R&amp;D services performance obligation. Therefore, we recognized the milestone payment in full in the third quarter of 2019.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471118" continuedAt="Text_34918020276946e4a34cbeb1b243c471119"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977120" continuedAt="Text_857e0866feaf4794bd379968f8751977121">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471119" continuedAt="Text_34918020276946e4a34cbeb1b243c471120"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977121" continuedAt="Text_857e0866feaf4794bd379968f8751977122">
<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;"><span style="text-decoration: underline;">License fees</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471120" continuedAt="Text_34918020276946e4a34cbeb1b243c471121"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977122" continuedAt="Text_857e0866feaf4794bd379968f8751977123">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471121" continuedAt="Text_34918020276946e4a34cbeb1b243c471122"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977123" continuedAt="Text_857e0866feaf4794bd379968f8751977124">
<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 generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. </span>For example, in the third quarter of 2019, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0fdd42612222445c956a5927b56c7f0a" contextRef="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million license fee when GSK licensed our HBV program from us.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977124" continuedAt="Text_857e0866feaf4794bd379968f8751977125"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471122" continuedAt="Text_34918020276946e4a34cbeb1b243c471123">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471123" continuedAt="Text_34918020276946e4a34cbeb1b243c471124"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977125" continuedAt="Text_857e0866feaf4794bd379968f8751977126">
<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;"><span style="text-decoration: underline;">Sublicense fees</span></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471124" continuedAt="Text_34918020276946e4a34cbeb1b243c471125"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977126" continuedAt="Text_857e0866feaf4794bd379968f8751977127">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471125" continuedAt="Text_34918020276946e4a34cbeb1b243c471126"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977127" continuedAt="Text_857e0866feaf4794bd379968f8751977128">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. </span>For example, in the second quarter of 2019, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6d686017b9d34c37a02641c0ee3ef4a8" contextRef="c20190401to20190630_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction> million sublicense fee when Alnylam Pharmaceuticals sublicensed our technology to Regeneron Pharmaceuticals.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471126" continuedAt="Text_34918020276946e4a34cbeb1b243c471127"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977128" continuedAt="Text_857e0866feaf4794bd379968f8751977129">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471127" continuedAt="Text_34918020276946e4a34cbeb1b243c471128"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977129" continuedAt="Text_857e0866feaf4794bd379968f8751977130">
<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_34918020276946e4a34cbeb1b243c471128" continuedAt="Text_34918020276946e4a34cbeb1b243c471129"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977130" continuedAt="Text_857e0866feaf4794bd379968f8751977131">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471129" continuedAt="Text_34918020276946e4a34cbeb1b243c471130"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977131" continuedAt="Text_857e0866feaf4794bd379968f8751977132">
<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_34918020276946e4a34cbeb1b243c471130" continuedAt="Text_34918020276946e4a34cbeb1b243c471131"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977132" continuedAt="Text_857e0866feaf4794bd379968f8751977133">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977133" continuedAt="Text_857e0866feaf4794bd379968f8751977134"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471131" continuedAt="Text_34918020276946e4a34cbeb1b243c471132">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd501d31562294c6aaa719422cd15d756">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977134" continuedAt="Text_857e0866feaf4794bd379968f8751977135"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471132" continuedAt="Text_34918020276946e4a34cbeb1b243c471133">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za3dd236033f64fc69c60fe14eb86f927">
  <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 at a stand-alone selling price. </div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471133" continuedAt="Text_34918020276946e4a34cbeb1b243c471134"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977135" continuedAt="Text_857e0866feaf4794bd379968f8751977136">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471134" continuedAt="Text_34918020276946e4a34cbeb1b243c471135"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977136" continuedAt="Text_857e0866feaf4794bd379968f8751977137">
<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 at their 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_34918020276946e4a34cbeb1b243c471135" continuedAt="Text_34918020276946e4a34cbeb1b243c471136"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977137" continuedAt="Text_857e0866feaf4794bd379968f8751977138">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>13</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471136" continuedAt="Text_34918020276946e4a34cbeb1b243c471137"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977138" continuedAt="Text_857e0866feaf4794bd379968f8751977139">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_04925e882d334a389a69c532092cf64b" contextRef="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">100</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_57a16aea2a5f41568fe5664de44e803a" contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with </span><ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_a00b0ca9a01345a49798907658fe58a8" contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_4db48f7dfeaa406aaa9d238c6b557cc8" contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million transaction price to these performance obligations. </span>Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for further discussion <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of our accounting treatment for our Bayer collaboration.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471137" continuedAt="Text_34918020276946e4a34cbeb1b243c471138"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977139" continuedAt="Text_857e0866feaf4794bd379968f8751977140">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471138" continuedAt="Text_34918020276946e4a34cbeb1b243c471139"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977140" continuedAt="Text_857e0866feaf4794bd379968f8751977141">
<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;">Multiple agreements</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471139" continuedAt="Text_34918020276946e4a34cbeb1b243c471140"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977141" continuedAt="Text_857e0866feaf4794bd379968f8751977142">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471140" continuedAt="Text_34918020276946e4a34cbeb1b243c471141"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977142" continuedAt="Text_857e0866feaf4794bd379968f8751977143">
<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_34918020276946e4a34cbeb1b243c471141" continuedAt="Text_34918020276946e4a34cbeb1b243c471142"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977143" continuedAt="Text_857e0866feaf4794bd379968f8751977144">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977144" continuedAt="Text_857e0866feaf4794bd379968f8751977145"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471142" continuedAt="Text_34918020276946e4a34cbeb1b243c471143">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z647b2221962b4885b6203f5375ade9eb">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977145" continuedAt="Text_857e0866feaf4794bd379968f8751977146"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471143" continuedAt="Text_34918020276946e4a34cbeb1b243c471144">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z24d42ec8f51f41848c8f9d33210e47e2">
  <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></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977146" continuedAt="Text_857e0866feaf4794bd379968f8751977147"><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471144" continuedAt="Text_34918020276946e4a34cbeb1b243c471145">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zf3b846712a0f4085b6899ba8ff04e10d">
  <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>
<div><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471145" continuedAt="Text_34918020276946e4a34cbeb1b243c471146"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977147" continuedAt="Text_857e0866feaf4794bd379968f8751977148">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471146" continuedAt="Text_34918020276946e4a34cbeb1b243c471147"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977148" continuedAt="Text_857e0866feaf4794bd379968f8751977149">
<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_34918020276946e4a34cbeb1b243c471147" continuedAt="Text_34918020276946e4a34cbeb1b243c471148"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977149" continuedAt="Text_857e0866feaf4794bd379968f8751977150">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_34918020276946e4a34cbeb1b243c471148"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977150" continuedAt="Text_857e0866feaf4794bd379968f8751977151">
<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_951a4e44e5184443bbbc525be5d8d3fb" 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_857e0866feaf4794bd379968f8751977151" continuedAt="Text_857e0866feaf4794bd379968f8751977152">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ReceivablesPolicyTextBlock" id="Text_c3bb5773b7744d1d8c746f80fd7e591e" contextRef="c20190101to20190930" escape="true" continuedAt="Text_343a415017cd4662b2c2881d499269b41"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977152" continuedAt="Text_857e0866feaf4794bd379968f8751977153">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_343a415017cd4662b2c2881d499269b41" continuedAt="Text_343a415017cd4662b2c2881d499269b42"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977153" continuedAt="Text_857e0866feaf4794bd379968f8751977154">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_343a415017cd4662b2c2881d499269b42"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977154" continuedAt="Text_857e0866feaf4794bd379968f8751977155">
<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 contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer</span>.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977155" continuedAt="Text_857e0866feaf4794bd379968f8751977156">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" id="Text_069517b639814bcfb63f346d7630c6ac" contextRef="c20190101to20190930" escape="true" continuedAt="Text_08041f09a00b437fbb47b14ce0af64a71"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977156" continuedAt="Text_857e0866feaf4794bd379968f8751977157">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_08041f09a00b437fbb47b14ce0af64a71" continuedAt="Text_08041f09a00b437fbb47b14ce0af64a72"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977157" continuedAt="Text_857e0866feaf4794bd379968f8751977158">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_08041f09a00b437fbb47b14ce0af64a72"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977158" continuedAt="Text_857e0866feaf4794bd379968f8751977159">
<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><ix:continuation id="Text_857e0866feaf4794bd379968f8751977159" continuedAt="Text_857e0866feaf4794bd379968f8751977160">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:RevenueRecognitionPolicyTextBlock" id="Text_39e2f330f3084a75956000480f2ecc99" contextRef="c20190101to20190930" escape="true" continuedAt="Text_8ae0fdc027044b55a214419e5d82a65a1"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977160" continuedAt="Text_857e0866feaf4794bd379968f8751977161">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_8ae0fdc027044b55a214419e5d82a65a1" continuedAt="Text_8ae0fdc027044b55a214419e5d82a65a2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977161" continuedAt="Text_857e0866feaf4794bd379968f8751977162">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8ae0fdc027044b55a214419e5d82a65a2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977162" continuedAt="Text_857e0866feaf4794bd379968f8751977163">
<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 September 30, 2019 and 2018, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_29a96e3cb4bb4440a9a1b2cd97733561" contextRef="c20190701to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">30.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_73cbcf1185e94594bcdf73d446b1e5e5" contextRef="c20180701to20180930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">37.2</ix:nonFraction> million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the nine months ended&#xA0;September 30, 2019 and 2018, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_a85dd4d0434f48769d4fff65100bcda5" contextRef="c20190101to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">103.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_2a8b360fd3ed495c9f969e160446bfc8" contextRef="c20180101to20180930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">80.4</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_857e0866feaf4794bd379968f8751977163" continuedAt="Text_857e0866feaf4794bd379968f8751977164">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:CostOfSalesPolicyTextBlock" id="Text_9511d33e757a42678615f83b5df904ed" contextRef="c20190101to20190930" escape="true" continuedAt="Text_6545eabfd29445cb93da2bcc17a951d61"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977164" continuedAt="Text_857e0866feaf4794bd379968f8751977165">
<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 Products Sold</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_6545eabfd29445cb93da2bcc17a951d61" continuedAt="Text_6545eabfd29445cb93da2bcc17a951d62"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977165" continuedAt="Text_857e0866feaf4794bd379968f8751977166">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_6545eabfd29445cb93da2bcc17a951d62"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977166" continuedAt="Text_857e0866feaf4794bd379968f8751977167">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed a significant portion of the costs we incurred to produce the supply for each medicine we are using in the commercial launch as research and development expense. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We previously expensed $</span><ix:nonFraction name="ions:CostOfProductsSoldPreviouslyRecognized" id="Fact_629c487159874d51b46161e6540c21bc" contextRef="c20190701to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="ions:CostOfProductsSoldPreviouslyRecognized" id="Fact_f48bb0935b8d4e11b248cc586569cce9" contextRef="c20190101to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of costs to produce our products related to the product sales revenue we recognized in the</span>&#xA0;three and nine months ended September 30, 2019, respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977167" continuedAt="Text_857e0866feaf4794bd379968f8751977168">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>14</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" id="Text_ece58b8638f04f80b592393388f33955" contextRef="c20190101to20190930" escape="true" continuedAt="Text_f749992bb04846f88fdeebfba95af8061"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977168" continuedAt="Text_857e0866feaf4794bd379968f8751977169">
<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;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_f749992bb04846f88fdeebfba95af8061" continuedAt="Text_f749992bb04846f88fdeebfba95af8062"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977169" continuedAt="Text_857e0866feaf4794bd379968f8751977170">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_f749992bb04846f88fdeebfba95af8062"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977170" continuedAt="Text_857e0866feaf4794bd379968f8751977171">
<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 Akcea&#8217;s IPO in July 2017, we owned <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_49ec7aa8448b4fb0b636f5c2fe809db9" contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent of Akcea. From the closing of Akcea&#8217;s IPO in July 2017 through mid-April 2018, we owned approximately <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_81e8ac19a87e4559825f24f967199b25" contextRef="c20170731_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_b04aa9a84ce140dca193528dabe7b2cb" contextRef="c20180430_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">68</ix:nonFraction></ix:nonFraction> percent of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L<sub>Rx</sub> to Akcea, increasing our ownership percentage to approximately <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_e1b36786245e4275887232820b2e06fe" contextRef="c20181231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">75</ix:nonFraction> percent. In the first quarter of 2019, we received <ix:nonFraction name="ions:ReceiptOfSharesInSubsidiary" id="Fact_8b20e19d078640888d7f1ed4020bb7f3" contextRef="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6">2.8</ix:nonFraction> million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_f1e0676599514d149a1144c81232642a" contextRef="c20190331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">76</ix:nonFraction> percent at March 31, 2019. At September 30, 2019, our ownership in Akcea was approximately <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_7c3a0c41d54d4122873d416c91a6bbe6" contextRef="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">75</ix:nonFraction> percent. In the fourth quarter of 2019, we expect to receive an additional <ix:nonFraction name="ions:ReceiptOfSharesInSubsidiary" id="Fact_d912ac6eeb764ab5a965714886e7f654" contextRef="c20191001to20191231_OwnershipAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.9</ix:nonFraction> million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx</sub>. We reflect changes in our ownership of Akcea in our financial statements as an adjustment to noncontrolling interest in the period the change occurs. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The shares third parties own represent an interest in Akcea&#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977171" continuedAt="Text_857e0866feaf4794bd379968f8751977172">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock" id="Text_cac3a0042b7c4b1fba021dd7fa0e0a6f" contextRef="c20190101to20190930" escape="true" continuedAt="Text_ebad976f5bd34c3ab17bf9f0c9f260061"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977172" continuedAt="Text_857e0866feaf4794bd379968f8751977173">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_ebad976f5bd34c3ab17bf9f0c9f260061" continuedAt="Text_ebad976f5bd34c3ab17bf9f0c9f260062"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977173" continuedAt="Text_857e0866feaf4794bd379968f8751977174">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ebad976f5bd34c3ab17bf9f0c9f260062" continuedAt="Text_ebad976f5bd34c3ab17bf9f0c9f260063"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977174" continuedAt="Text_857e0866feaf4794bd379968f8751977175">
<div 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. We use the specific identification method to determine the cost of securities sold.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ebad976f5bd34c3ab17bf9f0c9f260063" continuedAt="Text_ebad976f5bd34c3ab17bf9f0c9f260064"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977175" continuedAt="Text_857e0866feaf4794bd379968f8751977176">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ebad976f5bd34c3ab17bf9f0c9f260064"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977176" continuedAt="Text_857e0866feaf4794bd379968f8751977177">
<div 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 September 30, 2019, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8037e90f29fb43ae9797ff009a688387" contextRef="c20190930" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_42a31c163e8a40a8894a3145e0b1c651" contextRef="c20190930" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977177" continuedAt="Text_857e0866feaf4794bd379968f8751977178">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:InventoryPolicyTextBlock" id="Text_31e43aa1cfc849aebac03eff56f0c301" contextRef="c20190101to20190930" escape="true" continuedAt="Text_8046aed881b74f9abf12bf69396837741"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977178" continuedAt="Text_857e0866feaf4794bd379968f8751977179">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_8046aed881b74f9abf12bf69396837741" continuedAt="Text_8046aed881b74f9abf12bf69396837742"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977179" continuedAt="Text_857e0866feaf4794bd379968f8751977180">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8046aed881b74f9abf12bf69396837742" continuedAt="Text_8046aed881b74f9abf12bf69396837743"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977180" continuedAt="Text_857e0866feaf4794bd379968f8751977181">
<div 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 market 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. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8046aed881b74f9abf12bf69396837743" continuedAt="Text_8046aed881b74f9abf12bf69396837744"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977181" continuedAt="Text_857e0866feaf4794bd379968f8751977182">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8046aed881b74f9abf12bf69396837744" continuedAt="Text_8046aed881b74f9abf12bf69396837745"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977182" continuedAt="Text_857e0866feaf4794bd379968f8751977183">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained the first regulatory approval for TEGSEDI in July 2018 and in May 2019 for WAYLIVRA. At September 30, 2019, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;D expenses.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8046aed881b74f9abf12bf69396837745" continuedAt="Text_8046aed881b74f9abf12bf69396837746"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977183" continuedAt="Text_857e0866feaf4794bd379968f8751977184">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8046aed881b74f9abf12bf69396837746" continuedAt="Text_8046aed881b74f9abf12bf69396837747"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977184" continuedAt="Text_857e0866feaf4794bd379968f8751977185">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did </span><ix:nonFraction name="us-gaap:InventoryWriteDown" id="Fact_f8b23610178f4edc95899a9899da8223" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t record any material inventory write-offs for the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Total inventory was $</span><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_a25964c9ffea42bf8fc7de576a76596b" contextRef="c20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">19.4</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:InventoryNet" id="Fact_44dd20165015443893e9dc2dbfa04d40" contextRef="c20181231" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">8.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million as of </span>September 30, 2019 and December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977185" continuedAt="Text_857e0866feaf4794bd379968f8751977186"><ix:continuation id="Text_8046aed881b74f9abf12bf69396837747">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>15</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:LesseeLeasesPolicyTextBlock" id="Text_dab9a4f4745349fcabd0a7206f8be4ec" contextRef="c20190101to20190930" escape="true" continuedAt="Text_7345b1e43c924e4098da62c5bddb96081"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977186" continuedAt="Text_857e0866feaf4794bd379968f8751977187">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96081" continuedAt="Text_7345b1e43c924e4098da62c5bddb96082"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977187" continuedAt="Text_857e0866feaf4794bd379968f8751977188">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96082" continuedAt="Text_7345b1e43c924e4098da62c5bddb96083"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977188" continuedAt="Text_857e0866feaf4794bd379968f8751977189">
<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;">Topic 842 Adoption</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96083" continuedAt="Text_7345b1e43c924e4098da62c5bddb96084"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977189" continuedAt="Text_857e0866feaf4794bd379968f8751977190">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96084" continuedAt="Text_7345b1e43c924e4098da62c5bddb96085"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977190" continuedAt="Text_857e0866feaf4794bd379968f8751977191">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2016, the Financial Accounting Standards Board, or FASB, issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>, or Topic 840, and created a new lease accounting standard, Topic 842, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing lease, it will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $<ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_2e29b349bb85448f954a632df4428999" contextRef="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">13.5</ix:nonFraction> million in right-of-use operating lease assets and $<ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_182b919ed3e64fc4b0825beb4f643f7a" contextRef="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">18.5</ix:nonFraction> million in operating lease liabilities, of which we classified $<ix:nonFraction name="us-gaap:OperatingLeaseLiabilityCurrent" id="Fact_aa18508f1ac14387a7398aea8afb242c" contextRef="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">2</ix:nonFraction> million as a current liability. We adopted Topic 842 using the available practical expedients<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. </span>The adoption did not have an impact on our condensed consolidated statement of operations.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96085" continuedAt="Text_7345b1e43c924e4098da62c5bddb96086"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977191" continuedAt="Text_857e0866feaf4794bd379968f8751977192">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96086" continuedAt="Text_7345b1e43c924e4098da62c5bddb96087"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977192" continuedAt="Text_857e0866feaf4794bd379968f8751977193">
<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;">Leases</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96087" continuedAt="Text_7345b1e43c924e4098da62c5bddb96088"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977193" continuedAt="Text_857e0866feaf4794bd379968f8751977194">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96088" continuedAt="Text_7345b1e43c924e4098da62c5bddb96089"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977194" continuedAt="Text_857e0866feaf4794bd379968f8751977195">
<div 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.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#xA0;</span>We determined the lease term at the inception of the 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.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb96089" continuedAt="Text_7345b1e43c924e4098da62c5bddb960810"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977195" continuedAt="Text_857e0866feaf4794bd379968f8751977196">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_7345b1e43c924e4098da62c5bddb960810"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977196" continuedAt="Text_857e0866feaf4794bd379968f8751977197">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 or as of the lease inception date in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. 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_857e0866feaf4794bd379968f8751977197" continuedAt="Text_857e0866feaf4794bd379968f8751977198">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977198" continuedAt="Text_857e0866feaf4794bd379968f8751977199">
<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_857e0866feaf4794bd379968f8751977199" continuedAt="Text_857e0866feaf4794bd379968f8751977200">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977200" continuedAt="Text_857e0866feaf4794bd379968f8751977201">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:ResearchAndDevelopmentExpensePolicy" id="Text_83efbe2afbbc4a539b023aed0fc786c9" contextRef="c20190101to20190930" escape="true"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">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.</span></ix:nonNumeric></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977201" continuedAt="Text_857e0866feaf4794bd379968f8751977202">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977202" continuedAt="Text_857e0866feaf4794bd379968f8751977203">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:IntangibleAssetsFiniteLivedPolicy" id="Text_1afefe4da9aa4d7b9012855eb852c721" contextRef="c20190101to20190930" escape="true"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">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 United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.</span></ix:nonNumeric></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977203" continuedAt="Text_857e0866feaf4794bd379968f8751977204">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:IncomeTaxPolicyTextBlock" id="Text_25282174729d4998ab5c7a9816f3daef" contextRef="c20190101to20190930" escape="true" continuedAt="Text_6d11a2e1dee5428b824aa93d1426e65c1"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977204" continuedAt="Text_857e0866feaf4794bd379968f8751977205">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_6d11a2e1dee5428b824aa93d1426e65c1" continuedAt="Text_6d11a2e1dee5428b824aa93d1426e65c2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977205" continuedAt="Text_857e0866feaf4794bd379968f8751977206">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_6d11a2e1dee5428b824aa93d1426e65c2" continuedAt="Text_6d11a2e1dee5428b824aa93d1426e65c3"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977206" continuedAt="Text_857e0866feaf4794bd379968f8751977207">
<div 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><ix:continuation id="Text_6d11a2e1dee5428b824aa93d1426e65c3" continuedAt="Text_6d11a2e1dee5428b824aa93d1426e65c4"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977207" continuedAt="Text_857e0866feaf4794bd379968f8751977208">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_6d11a2e1dee5428b824aa93d1426e65c4"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977208" continuedAt="Text_857e0866feaf4794bd379968f8751977209">
<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 December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977209" continuedAt="Text_857e0866feaf4794bd379968f8751977210">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>16</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" id="Text_c8392968e6a441099a970062bcd082df" contextRef="c20190101to20190930" escape="true" continuedAt="Text_d2d8405022ad4abea2f4896af2bcb25a1"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977210" continuedAt="Text_857e0866feaf4794bd379968f8751977211">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_d2d8405022ad4abea2f4896af2bcb25a1" continuedAt="Text_d2d8405022ad4abea2f4896af2bcb25a2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977211" continuedAt="Text_857e0866feaf4794bd379968f8751977212">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_d2d8405022ad4abea2f4896af2bcb25a2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977212" continuedAt="Text_857e0866feaf4794bd379968f8751977213">
<div 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, right-of-use operating lease assets and patent costs acquired from third parties, 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_857e0866feaf4794bd379968f8751977213" continuedAt="Text_857e0866feaf4794bd379968f8751977214">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:UseOfEstimates" id="Text_bd277cfebfa84a259359328ea8ed2a76" contextRef="c20190101to20190930" escape="true" continuedAt="Text_c21d6f7abbf541128f331bdd013041321"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977214" continuedAt="Text_857e0866feaf4794bd379968f8751977215">
<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;">Use of Estimates</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_c21d6f7abbf541128f331bdd013041321" continuedAt="Text_c21d6f7abbf541128f331bdd013041322"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977215" continuedAt="Text_857e0866feaf4794bd379968f8751977216">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_c21d6f7abbf541128f331bdd013041322"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977216" continuedAt="Text_857e0866feaf4794bd379968f8751977217">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977217" continuedAt="Text_857e0866feaf4794bd379968f8751977218">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_2da7bfa9547f4a7dbb2f9930781fb07b" contextRef="c20190101to20190930" escape="true" continuedAt="Text_fea2c94e724e46e3be3621a863e4da301"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977218" continuedAt="Text_857e0866feaf4794bd379968f8751977219">
<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;">Basic and Diluted Net Income (Loss) Per Share</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da301" continuedAt="Text_fea2c94e724e46e3be3621a863e4da302"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977219" continuedAt="Text_857e0866feaf4794bd379968f8751977220">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da302" continuedAt="Text_fea2c94e724e46e3be3621a863e4da303"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977220" continuedAt="Text_857e0866feaf4794bd379968f8751977221">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net income (loss) per share</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da303" continuedAt="Text_fea2c94e724e46e3be3621a863e4da304"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977221" continuedAt="Text_857e0866feaf4794bd379968f8751977222">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da304" continuedAt="Text_fea2c94e724e46e3be3621a863e4da305"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977222" continuedAt="Text_857e0866feaf4794bd379968f8751977223">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da305" continuedAt="Text_fea2c94e724e46e3be3621a863e4da306"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977223" continuedAt="Text_857e0866feaf4794bd379968f8751977224">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da306" continuedAt="Text_fea2c94e724e46e3be3621a863e4da307"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977224" continuedAt="Text_857e0866feaf4794bd379968f8751977225">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da307" continuedAt="Text_fea2c94e724e46e3be3621a863e4da308"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977225" continuedAt="Text_857e0866feaf4794bd379968f8751977226">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977226" continuedAt="Text_857e0866feaf4794bd379968f8751977227"><ix:nonNumeric name="us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" id="Text_8d8b0369ff0848a090cf672c2c7b5324" contextRef="c20190101to20190930" escape="true" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f51"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da308" continuedAt="Text_fea2c94e724e46e3be3621a863e4da309">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>
</ix:continuation></ix:nonNumeric></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977227" continuedAt="Text_857e0866feaf4794bd379968f8751977228"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da309" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3010"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f51" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f52">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977228" continuedAt="Text_857e0866feaf4794bd379968f8751977229"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3010" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3011"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f52" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f53">
<table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" 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;">Three months ended September 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</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: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: 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:WeightedAverageNumberOfSharesOwnedInSubsidiary" id="Fact_43c87bc87ac5417fbf0a113ba2c3234a" contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">70,221</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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:EarningsPerShareBasic" id="Fact_ce3442e281e8408982b337f4368ffcf2" contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.34</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_2ec32aecd2af4dc1a8b56a25f22107df" contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">23,772</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: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_79895e95b2894e3eb06f1387172f7322" contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">23,772</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net 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%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3ae9d4e6a9164c458bd06e9241ed229f" contextRef="c20190701to20190930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">49,930</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_57bf878287e349068e6f30c6291cbee9" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,158</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <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:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_a141a342ad8243d89879365ffd24543f" contextRef="c20190701to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,551</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_4c76f7f37884447aa99306b954311210" contextRef="c20190701to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.19</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977229" continuedAt="Text_857e0866feaf4794bd379968f8751977230"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3011" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3012"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f53" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f54">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3012" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3013"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f54" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f55"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977230" continuedAt="Text_857e0866feaf4794bd379968f8751977231">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3013" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3014"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f55" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f56"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977231" continuedAt="Text_857e0866feaf4794bd379968f8751977232">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3014" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3015"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f56" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f57"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977232" continuedAt="Text_857e0866feaf4794bd379968f8751977233">
<table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" 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;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</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: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: 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:WeightedAverageNumberOfSharesOwnedInSubsidiary" id="Fact_147163d75a3b4ff496d72c16efd9604d" contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">69,681</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_e8d0fd372c814f06a8e5e97032b606c0" contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.40</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_bf9ab4c5a403467d998d19366486515d" contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">28,174</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: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_1b364a5b33474bc8b9b91b217972d565" contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">28,174</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net 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%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_28ac53378e8446b29b2685ada729d8c7" contextRef="c20190101to20190930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">140,938</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_db3be26cc6a246d496d524251c4de3dd" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,764</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <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:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_ddea2641661a48a19609e7b6ab683674" contextRef="c20190101to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">139,800</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_d6aa6f0722e04f51922eb5ba015c6a45" contextRef="c20190101to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.81</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3015" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3016"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f57" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f58"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977233" continuedAt="Text_857e0866feaf4794bd379968f8751977234">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>17</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3016" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3017"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f58" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f59"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977234" continuedAt="Text_857e0866feaf4794bd379968f8751977235">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3017" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3018"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f59" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f510"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977235" continuedAt="Text_857e0866feaf4794bd379968f8751977236">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3018" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3019"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f510" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f511"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977236" continuedAt="Text_857e0866feaf4794bd379968f8751977237">
<table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" 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;">Three months ended September 30, 2018</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</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: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: 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:WeightedAverageNumberOfSharesOwnedInSubsidiary" id="Fact_35767e855cbf450cb21d26c324a1d927" contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">65,538</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:EarningsPerShareBasic" id="Fact_5e959d88aa6c46ca89a333d0d6cd3637" contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.73</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_b5a98a2a39f941be9021fd6378d498c6" contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">47,843</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: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b3c04982056e46bb89fc30c57b93d79c" contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">47,843</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net 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%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_0942c549bec2404c85d6c5d2d875dbfb" contextRef="c20180701to20180930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">43,226</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_12b944156d8e4b299dabc78291bbcf94" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,617</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <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:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_3690cd8d6cdf42c2b5de20022a93ff4c" contextRef="c20180701to20180930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">137,346</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_1dcf9ad2d573436e802c08844b4a926e" contextRef="c20180701to20180930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.03</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3019" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3020"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f511" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f512"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977237" continuedAt="Text_857e0866feaf4794bd379968f8751977238">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3020" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3021"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f512" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f513"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977238" continuedAt="Text_857e0866feaf4794bd379968f8751977239">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3021" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3022"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f513" continuedAt="Text_03ee632d14da4d70993a5d3cac0973f514"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977239" continuedAt="Text_857e0866feaf4794bd379968f8751977240">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3022" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3023"><ix:continuation id="Text_03ee632d14da4d70993a5d3cac0973f514"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977240" continuedAt="Text_857e0866feaf4794bd379968f8751977241">
<table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" 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;">Nine months ended September 30, 2018</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</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: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: 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:WeightedAverageNumberOfSharesOwnedInSubsidiary" id="Fact_ac3dd463ed9d4bf9862f1f070652c598" contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">57,347</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_69fbad8094384f33bc9707e3f6adbf24" contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">1.93</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_8650f31a880a4b12a608b1ceb7631a4c" contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">110,680</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: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_ae8e54757cd64b5b8d2cb242050b7e43" contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">110,680</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net 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%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_fe81f96af8d64d43aa22c9e8898d3879" contextRef="c20180101to20180930_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">67,517</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_7fc30ef6106c4f99b6f1d86ceb042c8b" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">43,163</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <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:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_6c28a82b0628460eb97a165705793181" contextRef="c20180101to20180930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">130,507</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_d812881305f747cb8ebb3e5bc9b3e57f" contextRef="c20180101to20180930" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.33</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3023" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3024"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977241" continuedAt="Text_857e0866feaf4794bd379968f8751977242">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3024" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3025"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977242" continuedAt="Text_857e0866feaf4794bd379968f8751977243">
<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;">Dilutive net income (loss per share)</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3025" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3026"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977243" continuedAt="Text_857e0866feaf4794bd379968f8751977244">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3026" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3027"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977244" continuedAt="Text_857e0866feaf4794bd379968f8751977245">
<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 and nine months ended&#xA0;September 30, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3027" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3028"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977245" continuedAt="Text_857e0866feaf4794bd379968f8751977246">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977246" continuedAt="Text_857e0866feaf4794bd379968f8751977247">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" id="Text_74b35ce2b59647fbbe22a05f5ef21ec6" contextRef="c20190101to20190930" escape="true" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e91"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3028" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3029"><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the three months ended September 30, 2019</span></ix:continuation></span></ix:nonNumeric><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e91" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e92"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3029" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3030"><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"> as follows (in thousands except per share amounts):</span></ix:continuation></span></ix:continuation></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977247" continuedAt="Text_857e0866feaf4794bd379968f8751977248"><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e92" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e93"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3030" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3031">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977248" continuedAt="Text_857e0866feaf4794bd379968f8751977249"><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e93" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e94"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3031" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3032">
<table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" 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;">Three months ended September 30, 2019</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;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" 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;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" 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;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" 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: 64%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_9fb5723a10994e27a024f7c1e5cd0716" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,158</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%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_050e301828d444f3a5653ffd4c563400" contextRef="c20190701to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,551</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:EarningsPerShareBasic" id="Fact_e8659768686445659dab6e86383833c8" contextRef="c20190701to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.19</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" 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:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" id="Fact_43f1a62c9c264928a56d300f48e9d197" contextRef="c20190701to20190930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U001" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" id="Fact_199c6529dde241af91e14231e1d53b18" contextRef="c20190701to20190930_AwardTypeAxis_RestrictedStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">844</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</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;">&#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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" id="Fact_e649c4d03de64d178fe31f34b49bc3cd" contextRef="c20190701to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">20</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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted" id="Fact_1a9febfa42664cc3a5b9c2e21b6dffbd" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,158</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_3c93baead1be4b60adcd866c0a05f9e6" contextRef="c20190701to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">143,408</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_90a490606f0b45dfae46401cba62173e" contextRef="c20190701to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.18</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977249" continuedAt="Text_857e0866feaf4794bd379968f8751977250"><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e94" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e95"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3032" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3033">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3033" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3034"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977250" continuedAt="Text_857e0866feaf4794bd379968f8751977251"><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e95" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e96">
<div 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 diluted net income per share for the nine months ended&#xA0;September 30, 2019 as follows (in thousands except per share amounts):</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3034" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3035"><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e96" continuedAt="Text_c38def9ec1904f16a2e1e9404ed878e97"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977251" continuedAt="Text_857e0866feaf4794bd379968f8751977252">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3035" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3036"><ix:continuation id="Text_c38def9ec1904f16a2e1e9404ed878e97"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977252" continuedAt="Text_857e0866feaf4794bd379968f8751977253">
<table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" 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;">Nine months ended September 30, 2019</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;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" 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;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" 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;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" 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: 64%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_6fbcb5c09e544300851e1b9a1c201df1" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,764</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%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_f32580286e3a408f963e4ee172e8de31" contextRef="c20190101to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">139,800</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:EarningsPerShareBasic" id="Fact_0274cd0035584f309cc5af4c1934a38c" contextRef="c20190101to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.81</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" 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:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" id="Fact_233e1fc3bc224a46bb0c8d1ffec44a84" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">2,208</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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: top; width: 64%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" id="Fact_b7b8c402d3364c1c852cbc2b08a43732" contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">793</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</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;">&#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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" id="Fact_7db7a12930ae4f64978bc31beb1673b8" contextRef="c20190101to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">20</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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted" id="Fact_c28e7de8515649e59a0392ea18d9cc55" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">112,764</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_2c961138725b4e11b0f070578b4446ec" contextRef="c20190101to20190930" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">142,821</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_d1af7642908b452fa7338a4148c5322d" contextRef="c20190101to20190930" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">0.79</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3036" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3037"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977253" continuedAt="Text_857e0866feaf4794bd379968f8751977254">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3037" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3038"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977254" continuedAt="Text_857e0866feaf4794bd379968f8751977255">
<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 and nine months ended&#xA0;September 30, 2019, the calculation excluded the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0328fad2a1ce4c8295b664c2611452cf" contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent notes because the effect on diluted earnings per share was anti-dilutive.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3038" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3039"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977255" continuedAt="Text_857e0866feaf4794bd379968f8751977256">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>18</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3039" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3040"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977256" continuedAt="Text_857e0866feaf4794bd379968f8751977257">
<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 and nine months ended September 30, 2018, 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_fea2c94e724e46e3be3621a863e4da3040" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3041"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977257" continuedAt="Text_857e0866feaf4794bd379968f8751977258">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977258" continuedAt="Text_857e0866feaf4794bd379968f8751977259"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3041" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3042">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5651e0539b1741fda1231d28f3d75c17">
  <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_5275256bfe3946a98fa9bdf2b057c890" contextRef="c20180930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent convertible senior notes;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977259" continuedAt="Text_857e0866feaf4794bd379968f8751977260"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3042" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3043">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z7e90304a08cb4b28bbe2c90004d5b48d">
  <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></div>
</div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977260" continuedAt="Text_857e0866feaf4794bd379968f8751977261"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3043" continuedAt="Text_fea2c94e724e46e3be3621a863e4da3044">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z503eee239a9647d2b0c553764a10ff4d">
  <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; and</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: left;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977261" continuedAt="Text_857e0866feaf4794bd379968f8751977262"><ix:continuation id="Text_fea2c94e724e46e3be3621a863e4da3044">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z7ddd358f5ffd49cb80e76497ec47f5cc">
  <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>
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977262" continuedAt="Text_857e0866feaf4794bd379968f8751977263">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:DebtPolicyTextBlock" id="Text_1b20b2d07f9247689a3647cff0f43791" contextRef="c20190101to20190930" escape="true" continuedAt="Text_2a21786b5c524e28b8a9bbabd506623b1"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977263" continuedAt="Text_857e0866feaf4794bd379968f8751977264">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_2a21786b5c524e28b8a9bbabd506623b1" continuedAt="Text_2a21786b5c524e28b8a9bbabd506623b2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977264" continuedAt="Text_857e0866feaf4794bd379968f8751977265">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_2a21786b5c524e28b8a9bbabd506623b2" continuedAt="Text_2a21786b5c524e28b8a9bbabd506623b3"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977265" continuedAt="Text_857e0866feaf4794bd379968f8751977266">
<div 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 convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_2a21786b5c524e28b8a9bbabd506623b3" continuedAt="Text_2a21786b5c524e28b8a9bbabd506623b4"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977266" continuedAt="Text_857e0866feaf4794bd379968f8751977267">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_2a21786b5c524e28b8a9bbabd506623b4"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977267" continuedAt="Text_857e0866feaf4794bd379968f8751977268">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977268" continuedAt="Text_857e0866feaf4794bd379968f8751977269">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:SegmentReportingPolicyPolicyTextBlock" id="Text_97000bfae13e42c39cc8a855b0475323" contextRef="c20190101to20190930" escape="true" continuedAt="Text_625b333de3f14810a8ad49a872dc642a1"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977269" continuedAt="Text_857e0866feaf4794bd379968f8751977270">
<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;">Segment Information</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_625b333de3f14810a8ad49a872dc642a1" continuedAt="Text_625b333de3f14810a8ad49a872dc642a2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977270" continuedAt="Text_857e0866feaf4794bd379968f8751977271">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_625b333de3f14810a8ad49a872dc642a2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977271" continuedAt="Text_857e0866feaf4794bd379968f8751977272">
<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 have </span><ix:nonFraction name="us-gaap:NumberOfOperatingSegments" id="Fact_84d558a052504679b86bda59ad2a4f16" contextRef="c20190101to20190930" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is </span>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977272" continuedAt="Text_857e0866feaf4794bd379968f8751977273">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy" id="Text_ea6ca4b7f7044d6782f4b675d057249a" contextRef="c20190101to20190930" escape="true" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad1"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977273" continuedAt="Text_857e0866feaf4794bd379968f8751977274">
<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:continuation></ix:nonNumeric><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad1" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977274" continuedAt="Text_857e0866feaf4794bd379968f8751977275">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad2" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad3"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977275" continuedAt="Text_857e0866feaf4794bd379968f8751977276">
<div 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, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>
</ix:continuation></ix:continuation><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" id="Text_64ff1eea8a674e2eac6b01877ceb01c0" contextRef="c20190101to20190930" escape="true" continuedAt="Text_ad455530059c40e4b434dfa594ebf1151"><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad3" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad4"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977276" continuedAt="Text_857e0866feaf4794bd379968f8751977277">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:nonNumeric><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad4" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad5"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977277" continuedAt="Text_857e0866feaf4794bd379968f8751977278"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1151" continuedAt="Text_ad455530059c40e4b434dfa594ebf1152">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#xA0;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad5" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad6"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1152" continuedAt="Text_ad455530059c40e4b434dfa594ebf1153"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977278" continuedAt="Text_857e0866feaf4794bd379968f8751977279">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad6" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad7"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1153" continuedAt="Text_ad455530059c40e4b434dfa594ebf1154"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977279" continuedAt="Text_857e0866feaf4794bd379968f8751977280">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Employee Stock Options:</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad7" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad8"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1154" continuedAt="Text_ad455530059c40e4b434dfa594ebf1155"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977280" continuedAt="Text_857e0866feaf4794bd379968f8751977281">
<table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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_10af540d1817417c9927ac644de4ac4c" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.3</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_451b15c5e6db4150adb1ddb93a747fb2" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.3</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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_297eca7f077046459d0098f137fbb6d6" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember" 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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_59881b4df8734e98b052671b23864c88" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember" 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%; background-color: #FFFFFF; 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_2d88dae4193a41ada295a101a912f525" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">60.3</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_708d6e06317848a7a06e027a64378a15" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">63.1</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; background-color: #FFFFFF;"><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; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_2f2c71447843446799e8b051562c8b3f" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">4.6</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_5a08032609f748cfba2fe024615effc1" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">4.6</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad8" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad9"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1155" continuedAt="Text_ad455530059c40e4b434dfa594ebf1156"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977281" continuedAt="Text_857e0866feaf4794bd379968f8751977282">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>19</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad9" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad10"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1156" continuedAt="Text_ad455530059c40e4b434dfa594ebf1157"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977282" continuedAt="Text_857e0866feaf4794bd379968f8751977283">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad10" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad11"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977283" continuedAt="Text_857e0866feaf4794bd379968f8751977284"><ix:continuation id="Text_ad455530059c40e4b434dfa594ebf1157">
<table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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_47a2bc7c231249cb96aa9c1e7fc3ba14" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">1.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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_a3b917e92a684736b97b9361a6e89260" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_74f46b234c9b4b0592f9f9845c4b3529" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember" 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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_aa7f24671daf4a33bf1c24cc18a0d2c5" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember" 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%; background-color: #FFFFFF; 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_82556525924847188c081c3c2196dcf4" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">60.7</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_a8374861397d4239a10dc05defdd1f9b" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">61.5</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; background-color: #FFFFFF;"><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; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_eca1a2da37344e12a31ea04c3331f2ce" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember" format="ixt-sec:duryear">6.6</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_948ea3d373ec4e10ae7d7a59d44b0757" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember" format="ixt-sec:duryear">6.6</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad11" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad12"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977284" continuedAt="Text_857e0866feaf4794bd379968f8751977285">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad12" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad13"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977285" continuedAt="Text_857e0866feaf4794bd379968f8751977286">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad13" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad14"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977286" continuedAt="Text_857e0866feaf4794bd379968f8751977287"><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" id="Text_e7cb432140054dd39e19ff74d588e147" contextRef="c20190101to20190930" escape="true">
<table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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_775464219ddd4ea6b2ba785c16cb7f08" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.4</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_5b82a427bfdc485da1b5bb39d49b314f" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">1.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_c9bb147cbfdc4bb082d8f58b49bb33c0" contextRef="c20190101to20190930_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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_9567f947bd664cf7a27759a728810797" contextRef="c20180101to20180930_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%; background-color: #FFFFFF; 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_8aec446124b44c97bbf119ee1c6f7505" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">45.6</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_ca689cbebb25416e94178e911ce5ebfa" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">47.3</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; background-color: #FFFFFF;"><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; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_210f045bca1e43768566651337659487" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_797105e5f7aa46deb02bda572ec70f0d" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:nonNumeric></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad14" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad15"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977287" continuedAt="Text_857e0866feaf4794bd379968f8751977288">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad15" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad16"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977288" continuedAt="Text_857e0866feaf4794bd379968f8751977289">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis RSU&#8217;s:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad16" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad17"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977289" continuedAt="Text_857e0866feaf4794bd379968f8751977290">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad17" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad18"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977290" continuedAt="Text_857e0866feaf4794bd379968f8751977291">
<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. RSUs vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_0c35355dc5634225ac4bb7af9fc81af7" contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The weighted-average grant date fair value of RSUs granted to employees for the nine months ended&#xA0;September 30, 2019 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_2ed34ba20cd24f5595aac11ba305ca5e" contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_EmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">59.79</ix:nonFraction> per share. The weighted-average grant date fair value of RSUs granted to our board of directors for the nine months ended&#xA0;September 30, 2019 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_7efd8b9385084843a70beff976ad9acd" contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_BoardOfDirectorsMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">64.65</ix:nonFraction> per share.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad18" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad19"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977291" continuedAt="Text_857e0866feaf4794bd379968f8751977292">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad19" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad20"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977292" continuedAt="Text_857e0866feaf4794bd379968f8751977293">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our stock plans, Akcea has its own stock plan under which it grants stock options and RSUs and under which it derives its stock-based compensation expense. <ix:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" id="Text_f70a5b3c31b0473c983800256b3d521d" contextRef="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" escape="true" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e1"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended</span></ix:nonNumeric><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e1" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e2"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">&#xA0;</span></ix:continuation></span><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e2" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e3"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">September 30, 2019</span></ix:continuation><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e3" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e4"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"> and 2018</span></ix:continuation><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e4" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e5"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">: </span></ix:continuation></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad20" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad21"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977293" continuedAt="Text_857e0866feaf4794bd379968f8751977294"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e5" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e6">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad21" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad22"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977294" continuedAt="Text_857e0866feaf4794bd379968f8751977295"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e6" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e7">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Akcea Employee Stock Options:</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad22" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad23"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977295" continuedAt="Text_857e0866feaf4794bd379968f8751977296"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e7" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e8">
<table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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_83c4f479e627437a8ab761fa8bf3a69a" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.3</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_8691f84664c942b1b7b9185a59c58075" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.7</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_95a75a9ed6b34013be503487dd5cf87a" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" 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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_e760013ba5754d128422890beed0eece" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" 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%; background-color: #FFFFFF; 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_3c6fea59822f4992b6a1b84e416c272e" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">75.6</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_246c29cdb32c42e6beab75d827c74d7c" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">77.1</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; background-color: #FFFFFF;"><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; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_d5f2e36fd00242239fa02d8d861049d1" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" format="ixt-sec:duryear">6.1</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_64c1243c6d064fa9b60c00bda01677a9" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" format="ixt-sec:duryear">6.1</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad23" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad24"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977296" continuedAt="Text_857e0866feaf4794bd379968f8751977297"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e8" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e9">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad24" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad25"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977297" continuedAt="Text_857e0866feaf4794bd379968f8751977298"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e9" continuedAt="Text_00f0978363244e02a8d28b72dd628d6e10">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Akcea Board of Directors Stock Options:</div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad25" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad26"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977298" continuedAt="Text_857e0866feaf4794bd379968f8751977299"><ix:continuation id="Text_00f0978363244e02a8d28b72dd628d6e10">
<table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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_e42a726c528e463fb0f682824f9c9d5f" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">1.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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_d8cfdb5bb9ce4e70a764224ec0b4869c" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_080be06e28754a408013be5db3ecf295" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" 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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_dd82d340bf5343ed9381feb15f5f2ff5" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" 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%; background-color: #FFFFFF; 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_e545bb0154bb4989b256872355a39745" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">73.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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_408e3218201b47959b2c28042225c8df" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">78.2</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_1fe1549d10fa427fa110919c148f3647" contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" format="ixt-sec:duryear">6.3</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_980c44c3f9d94688835c7289ec3d5cbc" contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" format="ixt-sec:duryear">6.4</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad26" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad27"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977299" continuedAt="Text_857e0866feaf4794bd379968f8751977300">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977300" continuedAt="Text_857e0866feaf4794bd379968f8751977301">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad27" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad28"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977301" continuedAt="Text_857e0866feaf4794bd379968f8751977302">
<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:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" id="Text_5defb28a8f684091ae59b0adb952202f" contextRef="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" escape="true" continuedAt="Text_0864d5d3960f432c9e32a3b3b9a7cdaa1"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;">Akcea ESPP:</span></ix:nonNumeric></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad28" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad29"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977302" continuedAt="Text_857e0866feaf4794bd379968f8751977303"><ix:continuation id="Text_0864d5d3960f432c9e32a3b3b9a7cdaa1">
<table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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_c70610c4ca26449d91c355ac8085f281" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">2.4</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_d22d8efec44a411f9761be66f7a5123c" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">1.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_bc12de55f91f4d44a80b4026b88edcc5" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" 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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_9985d2f174544df9b611b66bfe15d6b7" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" 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%; background-color: #FFFFFF; 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_8598c03331034b0cb4f7ed356fa02c75" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" 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;"><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_05881d8adb62457cb5b8270dbf6dcae0" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">64.2</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_da1d41e5da0145c89e8728b8a14fd2a6" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_08eb25ee394e44ee8e7f04f2ce1410fc" contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad29" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad30"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977303" continuedAt="Text_857e0866feaf4794bd379968f8751977304">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>20</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad30" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad31"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977304" continuedAt="Text_857e0866feaf4794bd379968f8751977305"><ix:nonNumeric name="us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" id="Text_7ed6498a86ce420cadfcc286dc339ff2" contextRef="c20190101to20190930" escape="true" continuedAt="Text_ffd34595eb384dbda485a416dfdfc4fa1">
<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 and nine months ended&#xA0;September 30, 2019 and 2018 (in thousands).</div>
</ix:nonNumeric></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad31" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad32"><ix:continuation id="Text_ffd34595eb384dbda485a416dfdfc4fa1" continuedAt="Text_ffd34595eb384dbda485a416dfdfc4fa2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977305" continuedAt="Text_857e0866feaf4794bd379968f8751977306">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad32" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad33"><ix:continuation id="Text_ffd34595eb384dbda485a416dfdfc4fa2"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977306" continuedAt="Text_857e0866feaf4794bd379968f8751977307">
<table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"></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;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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 rowspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Cost of products sold</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_8f8889793bc24130821266ebf7f8aedd" contextRef="c20190701to20190930_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">127</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_2415dad41b364b3dae6ff52d0689fc8b" contextRef="c20180701to20180930_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:AllocatedShareBasedCompensationExpense" id="Fact_192d34335f474b94af709bac4431ece0" contextRef="c20190101to20190930_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">383</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_cc18bcac872c4daf934b3a3d0edf9b5a" contextRef="c20180101to20180930_IncomeStatementLocationAxis_CostOfSalesMember" 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%; background-color: #FFFFFF;"><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</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_03800ecd1ad747d0aba2047e92b6de26" contextRef="c20190701to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">23,744</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_97b3b8e52bda42f08706655a30b1f9a5" contextRef="c20180701to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,780</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_9367ec0b16a34e4b94468ac1f96b68d2" contextRef="c20190101to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">71,935</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_28af0edf20b74afabc1e6a728bd3e5f1" contextRef="c20180101to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">57,698</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</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_4af22a8c725245f3bcdf01eb7210dd41" contextRef="c20190701to20190930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">255</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_70482a126d49429ead2cb0593dacedef" contextRef="c20180701to20180930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,103</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_7252e6e1733947739b14991b054d4f46" contextRef="c20190101to20190930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">39,246</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_66d7c1fc088a447491dc7c06b11c0013" contextRef="c20180101to20180930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">39,512</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total non-cash stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_df57d7e40de84153bb9ccd38c3cb39d0" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,126</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_54690c3115b5425ab6d0ed60da8683a1" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,883</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_cfcae472d24a41eba5315fc58eb907e1" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">111,564</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_6f949baf6d1140d588b155609b49e954" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">97,210</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad33" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad34"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977307" continuedAt="Text_857e0866feaf4794bd379968f8751977308">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977308" continuedAt="Text_857e0866feaf4794bd379968f8751977309"><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad34" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad35">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2019, <ix:nonFraction name="ions:NumberOfExecutiveOfficersTerminatingEmployment" id="Fact_3e2a0bb6aa7a475294a3bcc5865c7f50" contextRef="c20190701to20190930" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $<ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_8beef0e24089498c95b24a2166b6b643" contextRef="c20190701to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">19.1</ix:nonFraction> million of stock-based compensation expense it had previously recognized related to the executive officers&#8217; stock options and RSUs that were no longer going to vest.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977309" continuedAt="Text_857e0866feaf4794bd379968f8751977310"><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad35" continuedAt="Text_1aad28368d3f4005bc1d8ec06bbae0ad36">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_1aad28368d3f4005bc1d8ec06bbae0ad36"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977310" continuedAt="Text_857e0866feaf4794bd379968f8751977311">
<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 September 30, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_6097d64058bc441eb0e524a05dd8918d" contextRef="c20190930_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">143.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_125cca04b5d44104a490e2e882a60ceb" contextRef="c20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">71.3</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 non-vested stock options and RSUs over a weighted average amortization period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_d6b9842ffb434100bea3e5d18619ca48" contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">1.2</ix:nonNumeric> years and <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_4ff7e654f44947dc981e496d429a0f9e" contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.6</ix:nonNumeric> years, respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977311" continuedAt="Text_857e0866feaf4794bd379968f8751977312">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977312" continuedAt="Text_857e0866feaf4794bd379968f8751977313">
<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;">Amendment to Equity Plan</div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977313" continuedAt="Text_857e0866feaf4794bd379968f8751977314">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977314" continuedAt="Text_857e0866feaf4794bd379968f8751977315">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan to increase the total number of shares reserved for issuance under the plan from <ix:nonFraction name="us-gaap:CommonStockCapitalSharesReservedForFutureIssuance" id="Fact_2617bf4d91164bc58917be73b8a82e6d" contextRef="c20190531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">16</ix:nonFraction> million to <ix:nonFraction name="us-gaap:CommonStockCapitalSharesReservedForFutureIssuance" id="Fact_1570aaadc468443bbbdf1ec8cc7cbcc3" contextRef="c20190630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U001" decimals="-6" scale="6" format="ixt:numdotdecimal">23</ix:nonFraction> million shares.</div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977315" continuedAt="Text_857e0866feaf4794bd379968f8751977316">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977316" continuedAt="Text_857e0866feaf4794bd379968f8751977317">
<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;">Share Repurchase Program</div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977317" continuedAt="Text_857e0866feaf4794bd379968f8751977318">
<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_857e0866feaf4794bd379968f8751977318" continuedAt="Text_857e0866feaf4794bd379968f8751977319">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors approved an initial share repurchase program of up to $<ix:nonFraction name="us-gaap:StockRepurchaseProgramAuthorizedAmount1" id="Fact_81f917a2ff44449888840b8298801f93" contextRef="c20190930" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">125</ix:nonFraction> million of our common stock. Our stock repurchase program has no expiration date. To date, we have <ix:nonFraction name="us-gaap:StockRepurchasedDuringPeriodShares" id="Fact_3982585ef0f34f7184c70b3e49c11693" contextRef="c20190901to20190930" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction>t repurchased any shares of our common stock.</div>
</ix:continuation><ix:continuation id="Text_857e0866feaf4794bd379968f8751977319" continuedAt="Text_857e0866feaf4794bd379968f8751977320">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:nonNumeric name="us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock" id="Text_7bbc749ed0e449e5a4349828ccd31bda" contextRef="c20190101to20190930" escape="true" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce61"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977320" continuedAt="Text_857e0866feaf4794bd379968f8751977321">
<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;">Impact of Recently Issued Accounting Standards</div>
</ix:continuation></ix:nonNumeric><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce61" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce62"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977321" continuedAt="Text_857e0866feaf4794bd379968f8751977322">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce62" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce63"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977322" continuedAt="Text_857e0866feaf4794bd379968f8751977323">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce63" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce64"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977323" continuedAt="Text_857e0866feaf4794bd379968f8751977324">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce64" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce65"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977324" continuedAt="Text_857e0866feaf4794bd379968f8751977325">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. We plan to adopt this guidance on January 1, 2020 on a prospective basis. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce65" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce66"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977325" continuedAt="Text_857e0866feaf4794bd379968f8751977326">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce66" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce67"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977326" continuedAt="Text_857e0866feaf4794bd379968f8751977327">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce67" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce68"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977327" continuedAt="Text_857e0866feaf4794bd379968f8751977328">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>21</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce68" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce69"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977328" continuedAt="Text_857e0866feaf4794bd379968f8751977329">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce69" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce610"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977329" continuedAt="Text_857e0866feaf4794bd379968f8751977330">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977330" continuedAt="Text_857e0866feaf4794bd379968f8751977331"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce610" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce611">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z8bdd29a294eb40de9936181c921e770a">
  <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;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977331" continuedAt="Text_857e0866feaf4794bd379968f8751977332"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce611" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce612">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zcfd41a05fd534170aa5bf96451b5d895">
  <tr>
    <td style="width: 72pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer </div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977332" continuedAt="Text_857e0866feaf4794bd379968f8751977333"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce612" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce613">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z01a3ba1f007c4a6aa41b051b55d3c310">
  <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;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977333" continuedAt="Text_857e0866feaf4794bd379968f8751977334"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce613" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce614">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zf0bc1b58e5944c7c95ca172b59ca15bd">
  <tr>
    <td style="width: 72pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We will use the &#8220;unit of account&#8221; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977334" continuedAt="Text_857e0866feaf4794bd379968f8751977335"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce614" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce615">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z8b99d6ac86964c488e342898b48a042f">
  <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;">3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977335" continuedAt="Text_857e0866feaf4794bd379968f8751977336"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce615" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce616">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z991322bb7f8b47b487f7e37acfd889f8">
  <tr>
    <td style="width: 72pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction </div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_857e0866feaf4794bd379968f8751977336" continuedAt="Text_857e0866feaf4794bd379968f8751977337"><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce616" continuedAt="Text_199b0b1acdab4f668a2da0dc6cf96ce617">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_199b0b1acdab4f668a2da0dc6cf96ce617"><ix:continuation id="Text_857e0866feaf4794bd379968f8751977337">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it could have on our condensed consolidated financial statements and disclosures.</div>
</ix:continuation></ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="invest:InvestmentTextBlock" id="Text_40768e1867ba41969846e8cd090324fe" contextRef="c20190101to20190930" escape="true" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd1">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 0.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div>
</ix:nonNumeric><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd1" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd2">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd2" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd3">
<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 September 30, 2019, we had invested our excess cash primarily in debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd3" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd4">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd4" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd5"><ix:nonNumeric name="us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock" id="Text_323a4af8c563455381e38fef93df2fd6" contextRef="c20190101to20190930" escape="true" continuedAt="Text_cac68e3a504d43a6b62e676ac917337c1">
<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 September 30, 2019:</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd5" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd6"><ix:continuation id="Text_cac68e3a504d43a6b62e676ac917337c1" continuedAt="Text_cac68e3a504d43a6b62e676ac917337c2">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd6" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd7"><ix:continuation id="Text_cac68e3a504d43a6b62e676ac917337c2">
<table cellpadding="0" cellspacing="0" id="zcf07523367524c41877d56d489917e98" 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;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_4b3282e6abbf4694b90d56a12cb3a78d" contextRef="c20190101to20190930" format="ixt-sec:durwordsen">One year</ix:nonNumeric> or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="Fact_26a36804df4340729bec0b2f463acda4" contextRef="c20190930" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">69</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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_3bd993e525784a5398b297b7856fe228" contextRef="c20190101to20190930" format="ixt-sec:durwordsen">one year</ix:nonNumeric> but within <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3" contextRef="c20190101to20190930" format="ixt-sec:durwordsen">two years</ix:nonNumeric></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_b3c2ee50dd694d208197df43360458a9" contextRef="c20190930" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">22</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_812c571149d64b329fe4410606d76c7a" contextRef="c20190101to20190930" format="ixt-sec:durwordsen">two years</ix:nonNumeric> but within <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange3" id="Fact_f12cc57cfa544d218ac6c26f9aae5797" contextRef="c20190101to20190930" format="ixt-sec:durwordsen">three years</ix:nonNumeric></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:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" id="Fact_8cd01e7f5688446294ec6f1b2d7e38df" contextRef="c20190930" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;"><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; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_6217a171f5784696968b178278e97ffa" contextRef="c20190930" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd7" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd8">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd8" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd9">
<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 September 30, 2019, <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_7de0397396204971870c9dfa3dc16f94" contextRef="c20190930" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">91</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_34c87d75876e42c988ffebc06f56b6a3" contextRef="c20190101to20190930" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd9" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd10">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd10" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd11">
<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_76961a53695f4f95a3d6a5f61b8f01bd11" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd12">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd12" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd13">
<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 September 30, 2019, we had an ownership interest of less than 20 percent in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b7edbc55e46842cb916a4ced56279788" contextRef="c20190930" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8144a98eb4174391a5f3065f3f804da4" contextRef="c20190930" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> public companies with which we conduct business. The privately-held companies are Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly-traded companies are ProQR and ATL.</div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd13" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd14">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>22</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd14" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd15">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd15" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd16">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock" id="Text_47bb69b206dc4e2ebd8789c0e31c814a" contextRef="c20190101to20190930" escape="true" continuedAt="Text_55065c1517994a09b34cacb1032056941"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following is a summary of our investments (in thousands):</span></ix:nonNumeric></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd16" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd17"><ix:continuation id="Text_55065c1517994a09b34cacb1032056941" continuedAt="Text_55065c1517994a09b34cacb1032056942">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_55065c1517994a09b34cacb1032056942" continuedAt="Text_55065c1517994a09b34cacb1032056943"><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd17" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd18">
<table cellpadding="0" cellspacing="0" id="zb56166283a7847d5befc091adecaa6a1" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <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; 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;">September 30, 2019</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(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;">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;">Available-for-sale securities:</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <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_5bd44b202ba0488e976f0c108e51d72a" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">752,495</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_17a030f590644d8f919cc3773c831571" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,484</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_12cd7dcada8d4d749dcdb38763dcfc9d" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">148</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_cd161d6d584f420ea5c9ba9bc949efac" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">753,831</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_eab544f46afa456189480b40679240a9" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">176,589</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_17d9194567ba4b81925f2f92660cef1f" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">321</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_100c8ffc20284501a343132ae0ed8437" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" 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%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_98c570c1585942bea5d1f0188f766317" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">176,865</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_1f3e39cc38284f8aad73189eea7bbf14" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">331,371</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_55dede5be12f465e91cb1036a8898b74" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">264</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_c9141f4d41694e8689367b43adc2e88c" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">17</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_d3a9b4856c74472f9ddbaffca452fcbc" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">331,618</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_9f527800450b4ccfad702bd8b0ced078" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">33,986</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_8b5ee7831a314b079d162b364f8e4186" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_4c6fcccfdd674057a042456beb6f3b4d" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">27</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a799e2ee1db54e1394e1dd3f2b81d089" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">33,963</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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_9015169599984f5a9691efcc7214ed32" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,948</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_f8d38bdedc944fc0b4eb5d019b737d68" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_b8ed51c2f99b4ac79d540094c9b6e9b1" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_011150cb25224f2cb838d6f4cfff763a" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,948</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_9801fd693cf84c299d17cb204de46d5f" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,297,389</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_34f6c8bc39f14366836a79be09b712d4" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,073</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_066fd70a5e7f4cf9afd3f01bfd157e98" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">237</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_121922e704004fc1bdeee945857a1e7a" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,299,225</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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_78a409a549ef459db614b179f7ae1230" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">539,820</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_fabc4941e21c404ebacd6fdd93f57eee" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,108</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_65ec80b321254172b0facb9181d06ab3" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">161</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_1d9754280ce9468db41a9c1e5804f2eb" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">542,767</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_ea15651e08bd4b8b990074a9aa80683d" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">106,536</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_8cc45dce333042f88f9270fcb2c87584" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">101</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_22da9338810541e081cb24fd8d1addd4" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">137</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bf708a036d044664bf01de902fd726fb" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">106,500</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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_bed56c4d2fcd4a74a0a1ccb2d57c9639" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,692</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_ab2034269cfb4a7c85423cd3fab55733" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_bfeeeeed126d480cb63fc576abeed8ef" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">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;"><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_9c5f4db9e8c94424a80d08bf4752ae35" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,654</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_a40f4d8491b24020962dbd41df0b3f94" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,283</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_e8c2bf9cfc364442a2ce959566f9039c" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">25</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_291761b8778841229cce19ecec0f26b3" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_6d8b2363ee3e48939c0b94531ab5f6fb" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,302</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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_138aaf4a47a148d091cceb4ced2e1cfc" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">690,331</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_7ca671875f59463da04bcd431895b579" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,234</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_a3e30c4027b34e7188416b4d33de1f4d" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">342</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_43d557630d984789a8b9913da42427b3" contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">693,223</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_80f9e07c881d4103821ad1c51c0e34b7" contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,987,720</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_58fe11e40d404aa1bab2f9bfb3e4d0cd" contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,307</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_155bd2a74c99447da52604b6e0c458ef" contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">579</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_1701ea613a34400c8d6e2580b27dc25d" contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,992,448</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: '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: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_1f42a3296a8a46159ca5daccd95f28b8" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,212</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_bf6daa922cab48a5a56d8a8813257503" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_ca3f0a0ae7664efd944e9c8d18081b2f" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">606</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_d39acd6dd3b74a26881b8fe7d99c92de" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">606</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_7dd9273ab6134971a061f83f1f11e5f6" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,988,932</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_f83b46d066b74393b302c03f0bf7f101" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,307</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_1127e05a95f04c3da8e856ad5d562421" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,185</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_f922c5a697914128981c946e313052fd" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,993,054</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_76961a53695f4f95a3d6a5f61b8f01bd18" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd19"><ix:continuation id="Text_55065c1517994a09b34cacb1032056943" continuedAt="Text_55065c1517994a09b34cacb1032056944">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_55065c1517994a09b34cacb1032056944" continuedAt="Text_55065c1517994a09b34cacb1032056945"><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd19" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd20">
<table cellpadding="0" cellspacing="0" id="zf8befa7024ac4c7aaab0e6b0e3be21d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <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; 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;">December 31, 2018</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(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;">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;">Available-for-sale securities:</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: 18pt; 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;"><div style="font-family: '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_b181ed8da53647f8a6b292342a235f93" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">956,879</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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_bbd0aadb835946f18c00643e19a95d1b" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">13</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_ef0125a302774eefaaa95d7cf7c879a0" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,858</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_dbcc039edc834ac2bf7c0c255acc4867" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">955,034</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_0187b54b654f4e109666c7737fc2551d" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">168,839</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_ab76344cef7f4d43993f5ff521643328" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" 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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_b4681433116b4d49be98ad2b8e89cc78" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">104</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5e02db354e724de3836ccd8a4a92c759" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">168,738</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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_206242051e2c4d94b28d4e87712895a7" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">244,640</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_6f0457f7164444eb8b1dc2704dc0f245" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_62d4d48225f74aaaad2a2ad0173aa452" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">77</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_71837a554d3c4531a97fafd18eaeac73" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">244,578</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_1c044e91f5e742a3961b4f59ca6ef285" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">63,572</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_7d3ea0c7354749eb97f7cc78122944ce" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_2fce21e0f698443099b81320b4220f73" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">323</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c82b6d5a51574d56b98ea374c25e11c7" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">63,249</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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_15869a0e101243b38f48dfa9071509af" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,433,930</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_1a8eeeab3e9a48fc9b4e3403cac348d9" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">31</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_b203115e4d3d4e72b3822ecede585a5c" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,362</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><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_d0ad541f93a44b54b3991471f048623d" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,431,599</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_f4ce593384ef4b7d83aad4901d4548b6" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">299,018</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_a92b2d44b0c84e809a410e22bf4ced30" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">194</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_bf25c4a7182242d79e1b85dc2bf4e3a8" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,286</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7252bb5228e6422ea11010b94d8da62c" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">297,926</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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_9339c651e1c64d02a58d7ef8f3a401fa" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">107,789</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_9617460cdd5b45769ba45c19086e38d7" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">194</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-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_4f98c3bc34da499abc8824624efb172c" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">109</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_22bb9a4b97cf4246b6dc9bd0962a5b27" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">107,874</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_f4c2236cedf849b8971016981b4f39e6" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,600</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_d0ce355fb70e47d5923fc09d2c261c75" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_c490dce6cb514f82bda4675e80f535b2" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_086c2ee40cf648798b812f56d1a08d40" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,576</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_248f6769580b4861a0b529d0816594e0" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,980</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_39e13e8a0ade405ea0ac29e4ae20285f" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_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%; 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_3c8a38bab38d41a4ae260eea177fe99e" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">287</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_ef07e7ef74ef4549a8bfa4cccef332d1" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,693</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_2536445b56a5427d99424937cbc97ea6" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">439,387</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_1eaf51b48a72465da90436695575076e" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">388</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_9735663a68094d99915263b97c19d53d" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,706</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2de2853621774dc4bfc77ca8feee79e3" contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">438,069</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_cb912863d431429d957f3c945ccb7b83" contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,873,317</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_3e47e75bd6a34ec49729b7f1a089b5d8" contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">419</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_7ad5d8e4832145f791a6f372b747c076" contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,068</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fd5b6194ec48441eaeccfa14072ca7af" contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,869,668</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current 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_8433f3b9512246ac8207c5a05c776b60" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,212</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_ff3617eb3aa949b3bb85ba97180ca782" contextRef="c20180101to20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">137</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_c4705c14fdeb4bee9bbd4b73b126cd7a" contextRef="c20180101to20181231" 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_43027ad4163e4bf48b6d2e208cc4225b" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,349</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_db6494e7c50d4590bf5ea77988e0bd56" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,874,529</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_da3c037eece345dbb273716db26a5d65" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">556</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_0046e705d988481bb8e3da035ffe5c60" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,068</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_a9c78208c74f4e24ae95c6752970f890" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,871,017</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd20" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd21"><ix:continuation id="Text_55065c1517994a09b34cacb1032056945" continuedAt="Text_55065c1517994a09b34cacb1032056946">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;">
<div><ix:continuation id="Text_55065c1517994a09b34cacb1032056946" continuedAt="Text_55065c1517994a09b34cacb1032056947"><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd21" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd22">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze2689b040009421da56fad38f1ad9a5f">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_305e1d6b0b66460686148b2ce6e01d9b" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Our available-for-sale securities are held at amortized cost.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd22" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd23"><ix:continuation id="Text_55065c1517994a09b34cacb1032056947" continuedAt="Text_55065c1517994a09b34cacb1032056948">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;">
<div><ix:continuation id="Text_55065c1517994a09b34cacb1032056948" continuedAt="Text_55065c1517994a09b34cacb1032056949"><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd23" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd24">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4c2e520a6c644d0f8f16eee8ae381f87">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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></div>
</div>
<div><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd24" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd25"><ix:continuation id="Text_55065c1517994a09b34cacb1032056949" continuedAt="Text_55065c1517994a09b34cacb10320569410">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_55065c1517994a09b34cacb10320569410"><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd25" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd26">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z94b340357ef0469db6ab0f6c9e7f6ab9">
  <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_20cf8a92586d4d88bc45b040cb662025" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>23</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd26" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd27">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd27" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd28"><ix:nonNumeric name="us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" id="Text_0f4958e928884c1e9dea3a20663a4c54" contextRef="c20190101to20190930" escape="true" continuedAt="Text_4471c7247c9c439f8152f7277cfd81951">
<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 we consider to be temporarily impaired at September 30, 2019. 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.</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd28" continuedAt="Text_76961a53695f4f95a3d6a5f61b8f01bd29"><ix:continuation id="Text_4471c7247c9c439f8152f7277cfd81951" continuedAt="Text_4471c7247c9c439f8152f7277cfd81952">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_76961a53695f4f95a3d6a5f61b8f01bd29"><ix:continuation id="Text_4471c7247c9c439f8152f7277cfd81952">
<table cellpadding="0" cellspacing="0" id="z78a191fc6a1c47b5bbf4c2cc8e099df3" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;(In thousands)</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; 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:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" id="Fact_51b806ebffcc49c38f9a73201a064390" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U010" decimals="0" scale="0" format="ixt:numdotdecimal">104</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" id="Fact_0bc2c883bb864c4089ece35a15919bc3" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">304,705</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_83fd90d887664061be0bf9e1b69269ca" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">268</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" id="Fact_090ecc716c20432ba4efc5ca41020612" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">31,675</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_0291f3ece3d144e99e18bb05d715d423" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">41</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" id="Fact_df78e61e593749bdabb662abf7265e25" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">336,380</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" id="Fact_595a90051f0743fb8d4f51d27e54a83a" contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">309</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%; background-color: #FFFFFF; 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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" id="Fact_e08462cb68ac49b3b3c3359e5d770016" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U010" decimals="0" scale="0" format="ixt:numdotdecimal">28</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" id="Fact_cef3c9031cb54a4c9a576cfd6bb25f14" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">102,733</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_c24473498a7b43398e845fd91e459c33" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">156</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" id="Fact_3ae3c388e9a24270a821209f160a096b" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">22,974</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_8fe83f9b7aaf4ad6a7714928869b9022" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" id="Fact_4fa18bf2ef50415e95791a938f030095" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">125,707</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" id="Fact_25d35726c1ac4e569f145f5fac73d67b" contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" 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: #FFFFFF; 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:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" id="Fact_55d09cb2246149c9b30a133e2a92a05c" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U010" decimals="0" scale="0" format="ixt:numdotdecimal">9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" id="Fact_06735049f9934ec68599825699814a3f" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">77,918</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_4dc4d63e1a724eecb8a92758026dd667" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">55</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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" id="Fact_366d3d1a14dc46af8ca33eee848e6ef9" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_f463e65cbe1946d3a63d082c9b137caf" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" id="Fact_f3ea8fadc6484ec591933cb40c3852ea" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">77,918</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" id="Fact_30c82f5c0cc2433686b8fda2508a4229" contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">55</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%; padding-bottom: 2px; background-color: #FFFFFF; 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%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" id="Fact_373b2ec7bfcb4e44be7a438d30c91ea3" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U010" decimals="0" scale="0" format="ixt:numdotdecimal">13</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" id="Fact_e6f5865e27de4dbc86e5f379535eea9b" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,498</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_d12d239121ea48fa95cdbee79c23f439" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" id="Fact_294211c497a44b74b91d1241bde18b03" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,597</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_0288bef87a724fcaa157b07c499a7e33" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">32</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" id="Fact_c479a7699515486899d6561160d554b1" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">17,095</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" id="Fact_d586a1ba946e4a7c9681158315aba90b" contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">33</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" id="Fact_06f7abbf000f49eabde6e2071d5866cd" contextRef="c20190930" unitRef="U010" decimals="0" scale="0" format="ixt:numdotdecimal">154</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" id="Fact_b2bbc700ee75493eb9cd50059005c4e4" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">486,854</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_2b41934b661649a49df3fd610175613e" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">480</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" id="Fact_73bb0ba4579d45e58b41562b4b52041a" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">70,246</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_099dab2dd40b4d0fafc8c7b94d5e2019" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" id="Fact_13d5b5d23b744127821937d7996a7021" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">557,100</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" id="Fact_166f0b63c83849f2badec28280087aac" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">579</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>
</ix:continuation></ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_e78cc309d33646e099bb096d906cddfa" contextRef="c20190101to20190930" escape="true" continuedAt="Text_fb712f1dad374a28a1128a7944a407901">
<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_fb712f1dad374a28a1128a7944a407901" continuedAt="Text_fb712f1dad374a28a1128a7944a407902">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a407902" continuedAt="Text_fb712f1dad374a28a1128a7944a407903">
<div 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 the majority 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_fb712f1dad374a28a1128a7944a407903" continuedAt="Text_fb712f1dad374a28a1128a7944a407904">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a407904" continuedAt="Text_fb712f1dad374a28a1128a7944a407905"><ix:nonNumeric name="us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock" id="Text_d5bf395e71d644c394d9e335eb3fe054" contextRef="c20190101to20190930" escape="true" continuedAt="Text_fb932b49b7c4485fab371f1993b571b01">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that we regularly measure and carry at fair value. At </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions that extend to the fourth quarter of 2019; as a result, we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> The amount we owned in ProQR did not change from </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The tables below segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</span></div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a407905" continuedAt="Text_fb712f1dad374a28a1128a7944a407906"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b01" continuedAt="Text_fb932b49b7c4485fab371f1993b571b02">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a407906" continuedAt="Text_fb712f1dad374a28a1128a7944a407907"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b02" continuedAt="Text_fb932b49b7c4485fab371f1993b571b03">
<table cellpadding="0" cellspacing="0" id="ze035bc9b78a548a8a5fdecd96869b42a" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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_3e8681d673cb4651bd1fa1b44eaab381" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">202,904</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_e5fd125d4ce14e01ba945d09c22ca8f1" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">202,904</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_2ae7973768e94bfc95e7ace04ee2ee57" contextRef="c20190930_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_f06c4a25a92d4d4c8de1315bf85fd8ba" contextRef="c20190930_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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_26191d5384f64272905581a8fe8b850e" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,296,598</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_a95f5ccf79e94eacb1104c5c32c16f2c" contextRef="c20190930_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_005ea5438f1a425e8a7d2f6ca3f789f8" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,296,598</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_971bf29f6c974f35892eafb721742e6e" contextRef="c20190930_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_31607d0464414d63a9d40c3bda86cebd" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">283,365</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_e26d4a39eb374d97a569b01baf57ac91" contextRef="c20190930_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:AvailableForSaleSecurities" id="Fact_66ce550478994d1888c51ee65d3e1f4b" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">283,365</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_b25daef28f5b47418fe2948e4af478a7" contextRef="c20190930_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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_7e9a01d143344a90abd0d3c282087ea8" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">366,272</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_74bd8f38d6cb4e46a4682239ac10752a" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">366,272</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_0a74a6aa5ded432f9a25a4dd4c8ff5f1" contextRef="c20190930_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_2c1c07732dce41c1a5692ffaf6f7eb8c" contextRef="c20190930_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_719745a58a2745968c9eec989ba98101" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">43,265</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_7d0b724cbe6b447fbe815dfa3325c1bf" contextRef="c20190930_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:AvailableForSaleSecurities" id="Fact_a74935eb997046d5b5e3885e886e4c50" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">43,265</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_7c85b2b200b64b4192a661395ad16c98" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_d28150ca7b45448fa25fbb6cd2de43d0" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,948</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_5a61795ec459452ead9ddd38ac0001dc" contextRef="c20190930_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_1a9f64e6bb854352a0cc51103b746ffb" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,948</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_88b4fe6d399242d7afa665095fb970ae" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (5)</div></div></td>
    <td colspan="1" 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_df377b1e9061452b8f3d582001e6a515" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">606</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_bf12a1b598f8409895330f9066de1b32" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <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_ad99c2d1e5a94c5ba9d5a036cc502ad7" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <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_27206d10cda844678b9284a21f0089ac" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">606</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: 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: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_a331dc8e64f14efa9335022e05100a1b" contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,195,958</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_e1395942b9544480802a3d41ed25d304" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">569,176</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_51287e35ae9647498fd94416292e645c" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,626,176</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_6c77bc755d97480da91f20c3c22c51d6" contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">606</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a407907" continuedAt="Text_fb712f1dad374a28a1128a7944a407908"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b03" continuedAt="Text_fb932b49b7c4485fab371f1993b571b04">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>24</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a407908" continuedAt="Text_fb712f1dad374a28a1128a7944a407909"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b04" continuedAt="Text_fb932b49b7c4485fab371f1993b571b05">
<table cellpadding="0" cellspacing="0" id="z210039b332e745bb8548fc2512c58d45" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2018</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_57ccf9920b8146f388ce592d258d1e8f" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">146,281</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_fea6987da44d4b7b9ae95d3cbe838bac" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">146,281</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_84311542bec446b5ae4092e88c1dc39c" contextRef="c20181231_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_d3a3f525a776438d93d0f6cd6072a582" contextRef="c20181231_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%; background-color: #FFFFFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (6)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_d2cf55f51c9147beb6d1c06acf8ed2dc" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,252,960</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_4119dc6c174e4de8b86dd778da98348e" contextRef="c20181231_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_7d8b8702ebaa49688da5775fe3f37558" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,252,960</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_ed3e7cbd1aa24ea4950df980878d1f0b" contextRef="c20181231_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_303ee7acffb64b30b37958792583e02d" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">276,612</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_ada275bc1e4f439cb01075d0aa3db7b1" contextRef="c20181231_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:AvailableForSaleSecurities" id="Fact_50adb0366138423898f832093af4dabf" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">276,612</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_dd2e5cc835fe4294b9a304420fef7c35" contextRef="c20181231_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%; background-color: #FFFFFF;"><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 (7)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_6e8ff7ac339a47ee87988299df92fe42" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">260,154</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_dc688c57298544adbac4c5b3cfbccac1" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">260,154</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_78b4ceecb8ed42df949cfc7aeb36254e" contextRef="c20181231_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_e760b857f262426eb869bf7c46221388" contextRef="c20181231_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%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_cf2cd8ea24c34a298b35a62e5c63fe49" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">79,942</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_cef740673b7c4b34ad1d1090f381a7ee" contextRef="c20181231_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:AvailableForSaleSecurities" id="Fact_dd870cb48a2c41e1a286050af4d48831" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">79,942</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div></div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_708e4a66c0db45a1856993da22f84254" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (5)</div></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_48764182e11a4bb5958ad2aaafc3c0c6" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,349</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_188a62f9e68047bcb08308421c122a02" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_fc0cb8b8e77f46a3a979063a7dfedc7b" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_dbab2b6be37643578962200ba9475ea0" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,349</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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_ef2b12ca5e5b4853a44a965cf2a0461c" contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,017,298</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_b34b60c6b5eb4dfdbfd60019ed7589b9" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">406,435</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_f797a4c0b00e4af6b8ed32a98a8235e3" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,609,514</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_d7e10e063db449559b0596c6cc218dbb" contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,349</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_fb712f1dad374a28a1128a7944a407909" continuedAt="Text_fb712f1dad374a28a1128a7944a4079010"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b05" continuedAt="Text_fb932b49b7c4485fab371f1993b571b06">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079010" continuedAt="Text_fb712f1dad374a28a1128a7944a4079011"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b06" continuedAt="Text_fb932b49b7c4485fab371f1993b571b07">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt; 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_fb712f1dad374a28a1128a7944a4079011" continuedAt="Text_fb712f1dad374a28a1128a7944a4079012"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b07" continuedAt="Text_fb932b49b7c4485fab371f1993b571b08">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b08" continuedAt="Text_fb932b49b7c4485fab371f1993b571b09"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079012" continuedAt="Text_fb712f1dad374a28a1128a7944a4079013">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbee9abbccdd54e73807b84f4e3b2b782">
  <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.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079013" continuedAt="Text_fb712f1dad374a28a1128a7944a4079014"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b09" continuedAt="Text_fb932b49b7c4485fab371f1993b571b010">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b010" continuedAt="Text_fb932b49b7c4485fab371f1993b571b011"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079014" continuedAt="Text_fb712f1dad374a28a1128a7944a4079015">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z438bdc6881aa4cb99b165b8919727dda">
  <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" continuedAt="Foot_fcd6eb64276e4992be5a11556144493a1">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_08e330d1065a49519e95b71b1366c2a4" contextRef="c20190930_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">16.6</ix:nonFraction></ix:footnote><ix:continuation id="Foot_fcd6eb64276e4992be5a11556144493a1"> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079015" continuedAt="Text_fb712f1dad374a28a1128a7944a4079016"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b011" continuedAt="Text_fb932b49b7c4485fab371f1993b571b012">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b012" continuedAt="Text_fb932b49b7c4485fab371f1993b571b013"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079016" continuedAt="Text_fb712f1dad374a28a1128a7944a4079017">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4a15bc1d737a430282eea21dc5b0bfb3">
  <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_e555e136aa274c8e882586614fcdf5b2" 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></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079017" continuedAt="Text_fb712f1dad374a28a1128a7944a4079018"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b013" continuedAt="Text_fb932b49b7c4485fab371f1993b571b014">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b014" continuedAt="Text_fb932b49b7c4485fab371f1993b571b015"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079018" continuedAt="Text_fb712f1dad374a28a1128a7944a4079019">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3864b9dae47f4db89495ac682873943c">
  <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_67f6ff09f4d443248a7bd7fe03ce1bd9" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_b6ffb9e1084140569608377a45c541ae1">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_ee5972ccabd947f08e866af02ecd032a" contextRef="c20190930_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.0</ix:nonFraction></ix:footnote><ix:continuation id="Foot_b6ffb9e1084140569608377a45c541ae1"> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079019" continuedAt="Text_fb712f1dad374a28a1128a7944a4079020"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b015" continuedAt="Text_fb932b49b7c4485fab371f1993b571b016">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b016" continuedAt="Text_fb932b49b7c4485fab371f1993b571b017"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079020" continuedAt="Text_fb712f1dad374a28a1128a7944a4079021">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb45245eabfe741ed8a9fa3ca3dc821f5">
  <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_f0cb78a83b31476988ccfd169edddb78" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079021" continuedAt="Text_fb712f1dad374a28a1128a7944a4079022"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b017" continuedAt="Text_fb932b49b7c4485fab371f1993b571b018">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b018" continuedAt="Text_fb932b49b7c4485fab371f1993b571b019"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079022" continuedAt="Text_fb712f1dad374a28a1128a7944a4079023">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd2f62bfc179a4c6ea80ab9be8baa40fe">
  <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_2009e9e101cd4940acd892bb1ca9a15f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_347ac782eafb4ae5ab5b9401cb8461bc1">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_37b19471b2774b12872f273581f1a2fc" contextRef="c20181231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">50.2</ix:nonFraction></ix:footnote><ix:continuation id="Foot_347ac782eafb4ae5ab5b9401cb8461bc1"> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079023" continuedAt="Text_fb712f1dad374a28a1128a7944a4079024"><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b019" continuedAt="Text_fb932b49b7c4485fab371f1993b571b020">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_fb932b49b7c4485fab371f1993b571b020"><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079024" continuedAt="Text_fb712f1dad374a28a1128a7944a4079025">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z28e1624d992e41cbb67711b300f91fbe">
  <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_f21495f28c8740a99946dade31b02bd8" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_a71eb02b1de14954b4d080f4e07e15821">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_555765ba22074b7c9579a23c07449fe0" contextRef="c20181231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">14.2</ix:nonFraction></ix:footnote><ix:continuation id="Foot_a71eb02b1de14954b4d080f4e07e15821"> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079025" continuedAt="Text_fb712f1dad374a28a1128a7944a4079026">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079026" continuedAt="Text_fb712f1dad374a28a1128a7944a4079027">
<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_fb712f1dad374a28a1128a7944a4079027" continuedAt="Text_fb712f1dad374a28a1128a7944a4079028">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_fb712f1dad374a28a1128a7944a4079028">
<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_4535354b3f1643ae9324af29ecc7467d" contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1 </ix:nonFraction>percent notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_08dde5b870bf48ad8f56230371fe5c23" contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">783.7</ix:nonFraction> million at September 30, 2019. 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:LesseeOperatingLeasesTextBlock" id="Text_d5c8c3f120884a79a71b128c745e4df5" contextRef="c20190101to20190930" escape="true" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Operating Leases</div>
</ix:nonNumeric><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd1" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd2">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd2" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd3">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to <ix:nonFraction name="ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" id="Fact_1329e55da4b24760858cff0f1661423a" contextRef="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>&#xA0;<ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_d173eb748a4244ab9218fe6c1006c150" contextRef="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> periods.</div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd3" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd4">
<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_ac54fc36475245788dd3d824aeb998bd4" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd5">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease additional office space and we sublease a portion of this space to Akcea. We lease this space under a non-cancelable operating lease with an initial term ending in June 2023 and an option to extend the lease for <ix:nonFraction name="ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" id="Fact_e9ff44ffc86e4cc792faf91f29186330" contextRef="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction>&#xA0;<ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_89235ac20a9447e28844342f084f8e0f" contextRef="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> period. The sublease with Akcea is eliminated in our condensed consolidated financial statements.</div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd5" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd6">
<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_ac54fc36475245788dd3d824aeb998bd6" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd7">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea entered into an operating lease agreement for office space located in Boston, Massachusetts for its new corporate headquarters in the second quarter of 2018. The lease commencement date was in August 2018 and Akcea took occupancy in September 2018. Akcea is leasing this space under a non-cancelable operating lease with an initial term ending after <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_b4040ba6c3a5449ca0431c78dadcc6f7" contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" format="ixt-sec:durmonth">123</ix:nonNumeric> months and an option to extend the lease for an additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_a62715aca02b493c9c7ae5090e0245e5" contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> term. Under the lease agreement, Akcea received a <ix:nonNumeric name="ions:LesseeOperatingLeasePeriodOfFreeRent" id="Fact_cf16c83c2adb47f3bbf9d36201ccc3d1" contextRef="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" format="ixt-sec:durwordsen">three-month</ix:nonNumeric> free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $<ix:nonFraction name="ions:LesseeOperatingLeaseAllowanceForTenantImprovements" id="Fact_536a376ef364487fab6f3719c345245d" contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.8</ix:nonFraction> million. Akcea provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $<ix:nonFraction name="ions:LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" id="Fact_c72b744673274b47a98716e4aa4f4f08" contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.4</ix:nonFraction> million, to be reduced to $<ix:nonFraction name="ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" id="Fact_0de0396ac4ed487d9be0855964bf2ad1" contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.8</ix:nonFraction> million on the third anniversary of the rent commencement date and to $<ix:nonFraction name="ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" id="Fact_353e61b09a0c4f77b8aaa58598b878ac" contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.2</ix:nonFraction> million on the fifth anniversary of the rent commencement date if Akcea meets certain conditions set forth in the lease at each such time.</div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd7" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd8">
<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_ac54fc36475245788dd3d824aeb998bd8" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd9">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include the extension options for these leases.</div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd9" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd10">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>25</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd10" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd11"><ix:nonNumeric name="ions:LesseeOperatingLeaseInformationTableTextBlock" id="Text_ec59cccffe8f4df08b9f20cfc91b55a6" contextRef="c20190101to20190930" escape="true" continuedAt="Text_e32a841333f7425fb76ce2bd8d11df0b1">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd11" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd12"><ix:continuation id="Text_e32a841333f7425fb76ce2bd8d11df0b1" continuedAt="Text_e32a841333f7425fb76ce2bd8d11df0b2">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd12" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd13"><ix:continuation id="Text_e32a841333f7425fb76ce2bd8d11df0b2" continuedAt="Text_e32a841333f7425fb76ce2bd8d11df0b3">
<table cellpadding="0" cellspacing="0" id="zf42106fcdfa447c3a605f18b4bb6c5cc" 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: center;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;">At September 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;">&#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: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_3068d59045b74301b2c28fc3dfb6b8be" contextRef="c20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">13.0</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: 88%; background-color: #FFFFFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities (2)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_fbe5ecbb80b44b659c35900b4d87399c" contextRef="c20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">17.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1" id="Fact_979be86519a0452db35a7400c2b1c9a0" contextRef="c20190930" format="ixt-sec:duryear">8.3</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent" id="Fact_877f6ec0003e46b59290f627dcea6e25" contextRef="c20190930" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">7.5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd13" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd14"><ix:continuation id="Text_e32a841333f7425fb76ce2bd8d11df0b3" continuedAt="Text_e32a841333f7425fb76ce2bd8d11df0b4">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_e32a841333f7425fb76ce2bd8d11df0b4" continuedAt="Text_e32a841333f7425fb76ce2bd8d11df0b5"><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd14" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd15">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z134ddf538270485d8e34269956271e23">
  <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_550ffd62f7c940f1b6c1073473427cdb" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in deposits and other assets on our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd15" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd16"><ix:continuation id="Text_e32a841333f7425fb76ce2bd8d11df0b5" continuedAt="Text_e32a841333f7425fb76ce2bd8d11df0b6">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="text-align: justify;">
<div><ix:continuation id="Text_e32a841333f7425fb76ce2bd8d11df0b6"><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd16" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd17">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb6759401030e41a8ab46de882c820315">
  <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_f913e9fa94634b87a1ff2c11bfad2e80" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_708c0c49d47f4358a375c8bfb0459c081">Current portion of $<ix:nonFraction name="us-gaap:OperatingLeaseLiabilityCurrent" id="Fact_04c209b55cd343c495d9204a38815493" contextRef="c20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.1</ix:nonFraction></ix:footnote><ix:continuation id="Foot_708c0c49d47f4358a375c8bfb0459c081"> million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</ix:continuation></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
</div>
<div><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd17" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd18">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd18" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd19">
<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 nine months ended&#xA0;September 30, 2019, we paid $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_a2930947c0364634811e32f2e71b5292" contextRef="c20190101to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.9</ix:nonFraction> million of rent payments, which was included in operating activities in our condensed consolidated statement of cash flows.</div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd19" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd20">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd20" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd21"><ix:nonNumeric name="us-gaap:ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" id="Text_755569525bde4238abc938fe9a8e90e4" contextRef="c20190101to20190930" escape="true" continuedAt="Text_03152904441a44cca3afdf64842603021">
<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 September 30, 2019, the payments for our operating lease liabilities are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd21" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd22"><ix:continuation id="Text_03152904441a44cca3afdf64842603021" continuedAt="Text_03152904441a44cca3afdf64842603022">
<div style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd22" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd23"><ix:continuation id="Text_03152904441a44cca3afdf64842603022">
<table cellpadding="0" cellspacing="0" id="zb029d562d7d14830957cb4fe63551490" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Remainder of 2019</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" id="Fact_b172fcbc56fa449ca8d311d79522445f" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">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: 88%; background-color: #FFFFFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Years ending December 31,</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2020</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" id="Fact_f4a841c5f2a14915b26977cb0a43cc9b" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,282</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: 88%; background-color: #FFFFFF;"><div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2021</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree" id="Fact_cff84cd8c71846e3b68b3b54a1d69862" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,019</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour" id="Fact_af6fa6ab476b4157b441eb23c40c8d5c" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,781</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive" id="Fact_40ac9e32ac7a4df78893b4b4cc07a061" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,520</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" id="Fact_95cde5b159734e08a7287dd63168ae8a" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,861</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: 88%; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_6ecec3f1c18d49d6a5973d40b99d7e6e" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,264</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imputed interest</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" id="Fact_76416dec037740b29c18f75520e91e34" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,533</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating lease liabilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:OperatingLeaseLiability" id="Fact_8ca379c9d8b245ba84f4ee7d1b392918" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">17,731</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_ac54fc36475245788dd3d824aeb998bd23" continuedAt="Text_ac54fc36475245788dd3d824aeb998bd24">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_ac54fc36475245788dd3d824aeb998bd24">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_a6f852dadc68455e9cc7cb478d765cce" contextRef="c20190701to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_462f8023ee66421ba3d584c023ecf0c0" contextRef="c20180701to20180930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.0</ix:nonFraction> million for the three months ended September 30, 2019 and 2018, respectively. Rent expense was $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_47f9cb5356444e72803cedfffb66b467" contextRef="c20190101to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_48776725679644ff8dd1226f92cf1642" contextRef="c20180101to20180930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.8</ix:nonFraction> million for the nine months ended&#xA0;September 30, 2019 and 2018, respectively.</div>
</ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:IncomeTaxDisclosureTextBlock" id="Text_8233d9a1816040bf91b26046eab26a3f" contextRef="c20190101to20190930" escape="true" continuedAt="Text_78931354fcb44ed2972aa8b6d02e123d1">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Income Taxes</div>
</ix:nonNumeric><ix:continuation id="Text_78931354fcb44ed2972aa8b6d02e123d1" continuedAt="Text_78931354fcb44ed2972aa8b6d02e123d2">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_78931354fcb44ed2972aa8b6d02e123d2">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 24.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded an income tax benefit of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_8c6a908e6b65434bbf024e17428ebae8" contextRef="c20190701to20190930" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">14.9</ix:nonFraction> million and an income tax expense of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_fd1879cce1214f218a3342996ae53ea4" contextRef="c20190101to20190930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">9.2</ix:nonFraction> million for the three and nine months ended&#xA0;September 30, 2019, compared to income tax expense of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_3f21749a48134a59948ddf0a532aac46" contextRef="c20180701to20180930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_e60a44889ada460787b6908260e5125e" contextRef="c20180101to20180930" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.8</ix:nonFraction> million for the same periods in 2018, respectively. The tax benefit recorded for the three months ended September 30, 2019 varies from what we would have recorded using the U.S. federal statutory rate primarily due to a state tax benefit resulting from our combined state tax filings with Akcea, estimated R&amp;D and orphan drug credits, excess tax benefits related to share-based compensation and a benefit related to a change in the estimated tax value of Akcea shares we received in 2018. The increase in our income tax expense for the nine months ended&#xA0;September 30, 2019, compared to the same period in 2018, was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019. We expect to utilize our deferred tax assets to partially offset our U.S. federal taxable income.</div>
</ix:continuation></div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>26</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:CollaborativeArrangementDisclosureTextBlock" id="Text_efed6362b719454ea6ffcb75e7594dba" contextRef="c20190101to20190930" escape="true" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61731">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7.&#160; Collaborative Arrangements and Licensing Agreements</div>
</ix:nonNumeric><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d61731" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61732">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d61732" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61733">
<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 collaborations with substantive changes during the first nine months of 2019 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2018.</span></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d61733" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61734">
<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_64e2dd576f1c4dc9a925f263c12d61734" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61735">
<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_64e2dd576f1c4dc9a925f263c12d61735" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61736">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d61736" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61737">
<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;">Biogen</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d61737" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61738">
<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_64e2dd576f1c4dc9a925f263c12d61738" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d61739">
<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 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. In</span> December 2017, we entered into a collaboration with Biogen to identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and Biogen are currently developing </span><ix:nonFraction name="ions:NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" id="Fact_92d0ca6977364d5fb2c03318547a94af" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> medicines under collaborations, including medicines to treat people with ALS, Alzheimer&#8217;s disease</span><sub>&#xA0;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 September 2019, we have received $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_944abe169d7a466fb4caf185b29d5162" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-8" scale="9" format="ixt:numdotdecimal">2.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion from our Biogen collaborations, including $</span><ix:nonFraction name="ions:UpfrontPaymentReceivedIncludingPurchaseOfStock" id="Fact_0d14be9af67b4d4a829caea6fe74e573" contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-9" scale="9" format="ixt:numdotdecimal">1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion we received from Biogen in the second quarter of 2018 for our 2018 strategic neurology collaboration.</span></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d61739" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617310">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617310" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617311"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_a4df729ae7b348b986a98b4bee6e087a" contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" escape="true" continuedAt="Text_1fad9c3977d14695bfa3ca794166c22a1">
<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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617311" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617312"><ix:continuation id="Text_1fad9c3977d14695bfa3ca794166c22a1" continuedAt="Text_1fad9c3977d14695bfa3ca794166c22a2">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617312" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617313"><ix:continuation id="Text_1fad9c3977d14695bfa3ca794166c22a2">
<table cellpadding="0" cellspacing="0" id="z20353bec45cf4f6e84901f27ae49c055" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; 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_58894b647a204f3f9befa22c21936367" contextRef="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">81.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8ef36b11d0eb42bbb715301764db5835" contextRef="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">70.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_ea81f77e846e484588deec9130e7b93b" contextRef="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">211.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_842a3d9227b24a00849b1d5adf642f22" contextRef="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">167.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_214320278a344f3c9dcdf624651e18a3" contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">25.5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7513f535453a470d9ce60f657eb441e0" contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">34.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2136a17c75884df48c7a85b6e0e70556" contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">81.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_da2c5324aca542a6a505108419820b49" contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">66.9</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 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_13c9d5dadf7e4112ba3699c18a26e515" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">107.2</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fca0b727314b4479925799d29f853712" contextRef="c20180701to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">104.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_3e28ae0133c44ae2852d1a6de979167d" contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">293.8</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_fe69625b03684bf9aab284fbd671bee2" contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">234.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27.1pt; 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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_46a53177bab6411dbfa4bacef3eacf19" contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">64</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_3f7d76bc791847c7bd8e878596274ee8" contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">72</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_0f0eb4fc60434512b4407e359598effe" contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">47</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_c6510891f3034be2ab38f94f3553a832" contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">58</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617313" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617314">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617314" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617315">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617315" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617316">
<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_64e2dd576f1c4dc9a925f263c12d617316" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617317">
<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;">2018 Strategic Neurology</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617317" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617318">
<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_64e2dd576f1c4dc9a925f263c12d617318" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617319">
<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 second quarter of 2019, we achieved <ix:nonFraction name="ions:NumberOfMilestonePaymentsAchieved" id="Fact_306c661c02c04f9ebb9f4e44c4a3ef08" contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> $<ix:nonFraction name="ions:MilestonePaymentsReceived" id="Fact_83943752e48341b1a621f6a843f1b50b" contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million milestone payments from Biogen when we advanced <ix:nonFraction name="ions:NumberOfNewTargetsAdvanced" id="Fact_6cc814e8a72149c396b34a68306be938" contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> new targets for unidentified neurological diseases<sub>&#xA0;</sub>under this collaboration. These milestone payments did not create new performance obligations because they are part of our original R&amp;D services performance obligation. Therefore, we included these amounts in our transaction price for our R&amp;D services performance obligation. We are recognizing revenue for our R&amp;D services performance obligation based on the percentage of completion. From inception through September 2019, we have included $<ix:nonFraction name="ions:PaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_c9ca4f94b0054470b5d3b3df32d7d8ea" contextRef="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">582</ix:nonFraction> million in payments in the transaction price for our R&amp;D services performance obligation under this collaboration. We currently estimate we will satisfy our performance obligation in June 2028.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617319" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617320">
<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_64e2dd576f1c4dc9a925f263c12d617320" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617321">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialMilestonePayment" id="Fact_67f7f7f5b5c846b3bd36d59706671233" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million if Biogen designates another target under this collaboration.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617321" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617322">
<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_64e2dd576f1c4dc9a925f263c12d617322" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617323">
<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;">2013 Strategic Neurology</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617323" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617324">
<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_64e2dd576f1c4dc9a925f263c12d617324" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617325">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2019, we achieved an $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_278c916db294450ba8ed188743359ff4" contextRef="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">8</ix:nonFraction> million milestone payment when Biogen initiated a Phase 1/2 study of ION859 (IONIS-LRRK2<sub>Rx</sub>) <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the treatment of people with Parkinson&#8217;s disease </span>under this collaboration. We concluded that this milestone payment was not related to our R&amp;D services performance obligation. Therefore, we recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3af7c5f8c38b42e0a18b8c97fb956a41" contextRef="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">8</ix:nonFraction> million milestone payment in full in the third quarter of 2019 because we do not have any performance obligations related to this payment.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617325" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617326">
<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_64e2dd576f1c4dc9a925f263c12d617326" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617327">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through September 2019, we have included $<ix:nonFraction name="ions:PaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_3ee9be7ea55d48379bcd6f6e6e3eca37" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">145</ix:nonFraction> million in total payments in the transaction price for our R&amp;D services performance obligation under this collaboration that we are recognizing over our estimated period of performance. We are recognizing revenue as we perform services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. In the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation. As of September 30, 2019, we have completed a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> significant portion of the research and development services. We expect to complete the remainder of our services in 2020. </span>As a result, we recorded a cumulative catch up adjustment of $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_26614eaf255c46349ca103734b10813b" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">16.5</ix:nonFraction> million to decrease revenue in the third quarter of 2019. We will recognize this amount over the estimated remaining period we will perform services.</div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>27</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617327" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617328">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617328" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617329">
<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_64e2dd576f1c4dc9a925f263c12d617329" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617330">
<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 second quarter of 2019, we achieved a $<ix:nonFraction name="ions:MilestonePaymentsReceived" id="Fact_9d2d8a0a28aa4ef487bf47e6509d20c5" contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million milestone payment from Biogen when we advanced IONIS-MAPT<sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for Alzheimer&#8217;s disease</span> under this collaboration. This milestone payment did not create a new performance obligation because it is part of our performance obligation to conduct development of IONIS-MAPT<sub>Rx</sub>. Therefore, we included the $<ix:nonFraction name="ions:MilestonePaymentsReceived" id="Fact_e04de81796d34701ac54d0d5074cc31e" contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million milestone payment in our transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. We are recognizing revenue for our IONIS-MAPT<sub>Rx</sub> development performance obligation based on the percentage of completion. From inception through September 2019, we have included $<ix:nonFraction name="ions:PaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_f0eadc680d4f468eb5d90137253d596f" contextRef="c20190930_ProductOrServiceAxis_IONISMAPTMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">25.5</ix:nonFraction> million in the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. We currently estimate we will satisfy our performance obligation in September 2020.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617330" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617331">
<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_64e2dd576f1c4dc9a925f263c12d617331" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617332">
<div 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 a separate performance obligation to perform R&amp;D services under this collaboration. We have allocated $<ix:nonFraction name="ions:PaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_f00ee12baddd4b159c3c46bb74880769" contextRef="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">40</ix:nonFraction> million in total payments to the transaction price for our R&amp;D services performance obligation. In the third quarter of 2019, we completed our R&amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. Biogen&#8217;s decision to accept the development candidate was not within our control. We were recognizing revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. Because Biogen accepted the development candidate, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_35c6d90d51304a699ec0b4ff52f71fcd" contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">6.3</ix:nonFraction> million of accelerated revenue in the third quarter of 2019.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617332" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617333">
<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_64e2dd576f1c4dc9a925f263c12d617333" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617334">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPotentialMilestonePayment" id="Fact_43169d472f8f443abcf67b8f14b7d246" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million if we advance a program under this collaboration.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617334" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617335">
<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_64e2dd576f1c4dc9a925f263c12d617335" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617336">
<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 nine months of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Biogen collaborations, except as noted above.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617336" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617337">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617337" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617338">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2019 and December 31, 2018<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_54ef69d3adc940c88647a751ad2a37ea" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">532.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_3014f578216c4b458dd9badfa79faf90" contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6">580.9</ix:nonFraction> million, respectively, related to our relationship with Biogen.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617338" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617339">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617339" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617340">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Commercialization Partners</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617340" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617341">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617341" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617342">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bayer</div>
</ix:continuation></div>
<div style="background-color: #FFFFFF;"><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617342" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617343">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617343" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617344">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize our programs targeting FXI for the treatment of clotting disorders. In October 2019, Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub> following positive clinical results and we earned a $<ix:nonFraction name="ions:MilestonePaymentEarned" id="Fact_dc8c3107d8ce4ebdac270c3f0ff2ebcd" contextRef="c20191001to20191031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment. At September 30, 2019, we determined that it was not probable that we could earn this milestone payment. As such, we did not recognize any revenue associated with it during the third quarter of 2019. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI program. From inception through September 2019, we have received over $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_effec1c7861e4fcaaf3668d229b3a3a9" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">175</ix:nonFraction> million from our Bayer collaboration, not including the $<ix:nonFraction name="ions:MilestonePaymentEarned" id="Fact_e49028a7e92b4b55b48f4a1666cdf1c3" contextRef="c20191001to20191031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment we earned in the fourth quarter of 2019.&#160; We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialMilestonePayment" id="Fact_bc59ef56d057411cac4515747dfabcd7" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction> million when Bayer initiates a Phase 3 study under the FXI program.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617344" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617345">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617345" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617346">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">GSK</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617346" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617347">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617347" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617348">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK includes <ix:nonFraction name="ions:NumberOfDrugsCurrentlyBeingAdvanced" id="Fact_e5fe0235f431492d97bebbcd2963aeae" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> drugs targeting hepatitis B virus, or HBV: IONIS-HBV<sub>Rx</sub> and IONIS-HBV-L<sub>Rx</sub>, which we designed to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program, for which we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f390941f4a55430abca54016f555f3e3" contextRef="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million license fee. From inception through September 2019, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_58c2a122def94572b3276f3836cd2035" contextRef="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">164</ix:nonFraction> million in payments under our collaboration with GSK, not including the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b9708436d19a450abd82842dddcbdaa4" contextRef="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million license fee, which we expect to receive in the fourth quarter of 2019. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialMilestonePayment" id="Fact_ef95c04dc3a44340bf6d97d697affc47" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">15</ix:nonFraction> million when GSK initiates a Phase 3 study for a drug under this program.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617348" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617349">
<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_64e2dd576f1c4dc9a925f263c12d617349" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617350">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified a new performance obligation when we granted GSK the license of the HBV program and assignment of related intellectual property rights in the third quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_161ceddd95c4478eacc930db8d53cd82" contextRef="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">25</ix:nonFraction> million license fee for the HBV program as revenue at that time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617350" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617351">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617351" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617352"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_ca41bb95cd8b4b73a468aa7441b6fcf1" contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" escape="true" continuedAt="Text_a29f0f386a3f4b1db93d63a81c6a75751">
<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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617352" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617353"><ix:continuation id="Text_a29f0f386a3f4b1db93d63a81c6a75751" continuedAt="Text_a29f0f386a3f4b1db93d63a81c6a75752">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617353" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617354"><ix:continuation id="Text_a29f0f386a3f4b1db93d63a81c6a75752">
<table cellpadding="0" cellspacing="0" id="z2a013d4519bd47b387164e642d8d6b5c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_62118ab0fb5d41899bb44d2f396b1371" contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">25.1</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c32a477653cb42b3811095ae7c0b7a98" contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_2b0d64696c9d44c7b8cc9d051d50e372" contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">25.3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_f9c94c8a3fa4457f848c945c207a2aa7" contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.5</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: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_86ab793c4c224a73978fdfde779f9da2" contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">15</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_e499255f52504257b795c29f5829ad9b" contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_d96294bd312f4da7823a8cf9ad798494" contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">4</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_4d8e0ebf8aa94654a87ade66752b201a" contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617354" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617355">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617355" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617356">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_376c42cf9e2f4f31b526f22998089e92" contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_01e151232773447992d835603dcc704f" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" unitRef="U002" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any deferred revenue from our relationship with GSK at September 30, 2019 or December 31, 2018.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617356" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617357">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>28</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: left;"><br /></div>
<div><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617357" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617358">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Roche</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617358" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617359">
<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_64e2dd576f1c4dc9a925f263c12d617359" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617360">
<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 have </span><ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_11cb1f3d6c7040af8c4d4c72dbbce13d" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> collaborations with Roche, </span><ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_e8d6e2aa98a3466aac6e1aeaf1ccbc87" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to develop treatments for Huntington's disease, or HD, and </span><ix:nonFraction name="ions:NumberOfCollaborationAgreements" id="Fact_ffdc56de69c144fc82abb9c50783b017" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. In December 2017, upon completion of the Phase 1/2 study of IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Roche exercised its option to license IONIS-HTT</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In October 2018, we entered into a collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. The first indication we plan to pursue is the treatment of patients with geographic atrophy, or GA, the advanced stage of dry age-related macular degeneration, or AMD. We are responsible for conducting a Phase 2 study in patients with dry AMD. In addition, we plan to evaluate the medicine for a severe and rare renal indication. </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> has the option to license IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> at the completion of these studies. Upon licensing, </span>Roche <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for all further global development, regulatory and commercialization activities and costs.</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through June 2019, we have received over $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_a75b275ae3ae4d478cf2ad99f17a9e99" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">220</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from our Roche collaborations, including $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9a8c764ff07144f7add61d4cd70c3360" contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payments we earned in the first quarter of 2019 when Roche dosed the first patient in a Phase 3 study for IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPotentialMilestonePayment" id="Fact_6ed199bf3e5f43e48862b62fa432c1b7" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Roche advances IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617360" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617361">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617361" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617362"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_70f1cbc4bcf74b46a1a8e0b1b6ed1541" contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" escape="true" continuedAt="Text_6c0727ae496b43c88a8ba00801c149431">
<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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617362" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617363"><ix:continuation id="Text_6c0727ae496b43c88a8ba00801c149431" continuedAt="Text_6c0727ae496b43c88a8ba00801c149432">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617363" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617364"><ix:continuation id="Text_6c0727ae496b43c88a8ba00801c149432">
<table cellpadding="0" cellspacing="0" id="z5a49728eb04942b281219a3239b033e8" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_0f6d4a3a012f4477984b11c4664e4b6c" contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">4.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b33165b5e9824fb5bba54918e9dbd6cb" contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_40961bc844ef4352995937f4f432fdb8" contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">52.3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_3ef89c7313ad4f87aae1296cbcfa821c" contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">5.4</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_bdf875a68c1f4ffaa35dfa990f2a93f6" contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_6691931c366f4281a20d83228c234ffd" contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_f856f221a2b74ddf90b424d562484c0f" contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_a5fbc85f1f0d43b38f7078592cf03649" contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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_64e2dd576f1c4dc9a925f263c12d617364" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617365">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617365" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617366">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our revenue in the first nine months of 2019 included $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_773b279d63474cd5a044713ffc198719" contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">35</ix:nonFraction> million of milestone payments we earned when Roche dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx</sub> in the first quarter of 2019. We recognized these milestone payments in full in the first quarter of 2019 because we do not have any performance obligations related to these milestone payments, as Roche is conducting the Phase 3 study of IONIS-HTT<sub>Rx</sub>.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617366" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617367">
<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_64e2dd576f1c4dc9a925f263c12d617367" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617368">
<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 nine months of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Roche collaborations.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617368" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617369">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617369" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617370">
<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 September 30, 2019 and December 31, 2018<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_ae98e83e6d254226924f58b342e8f0e9" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">56.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_3e86da011f2d4ec7bc14c905d451cb50" contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">72.6</ix:nonFraction> million, respectively, related to our relationship with Roche.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617370" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617371">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617371" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617372">
<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;">Akcea Collaborations</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617372" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617373">
<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_64e2dd576f1c4dc9a925f263c12d617373" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617374">
<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 collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under this collaboration agreement. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617374" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617375">
<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_64e2dd576f1c4dc9a925f263c12d617375" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617376">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Novartis</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617376" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617377">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617377" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617378">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and AKCEA-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span><sub>&#xA0;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and AKCEA-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the FDA and providing initial quantities of API for each medicine. If Novartis exercises an option for either of these medicines, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such medicine. </span>In the first quarter of 2019, Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>. Novartis is responsible for conducting and funding all future development, regulatory and commercialization activities for AKCEA-APO(a)-L<sub>Rx</sub>, including a global pivotal cardiovascular outcomes study, for which planning and initiation activities are underway. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through September 2019, we have received over $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_3f1db703e5e04c3eba7f0303bd0307d8" contextRef="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">343</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from our Novartis collaboration, including $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8580e2d4500c4bcf9a63681481619efb" contextRef="c20190101to20190331_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">150</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we earned from Novartis in the first quarter of 2019 for the license of AKCEA-APO(a)-L</span><sub>Rx</sub>. Akcea paid us $<ix:nonFraction name="ions:SublicenseFeePaidForLicenseOfDrug" id="Fact_e1bd72cf7fb34dc588200203887e0e24" contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million as a sublicense fee in <ix:nonFraction name="ions:ReceiptOfSharesInSubsidiary" id="Fact_feb287ac8b2c4388941e91c3a3a53636" contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">2.8</ix:nonFraction> million shares of Akcea common stock.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617378" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617379">
<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_64e2dd576f1c4dc9a925f263c12d617379" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617380">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified a new performance obligation when we granted Novartis the license of AKCEA-APO(a)-L<sub>Rx</sub> in the first quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_decb57be15eb48b3a29939a7a5584f39" contextRef="c20190101to20190331_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">150</ix:nonFraction> million license fee for AKCEA-APO(a)-L<sub>Rx</sub> as revenue at that time because Novartis had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Novartis.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617380" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617381">
<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_64e2dd576f1c4dc9a925f263c12d617381" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617382">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis has the option to purchase additional API of AKCEA-APO(a)-L<sub>Rx</sub> in the future at agreed upon terms and conditions under our collaboration agreement. We identified a new performance obligation when we delivered additional AKCEA-APO(a)-L<sub>Rx</sub> API to Novartis in the third quarter of 2019 because the delivery of the API is distinct from our other performance obligations. We recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a01e8b882d20413eae3ece2fe5028d14" contextRef="c20190701to20190930_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">5.5</ix:nonFraction>&#160; million in revenue for the API we sold to Novartis in the third quarter of 2019.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617382" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617383">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>29</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617383" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617384">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea is responsible for the development activities under this collaboration. As such, Akcea is recognizing the associated revenue in its statement of operations, and we reflect all of Akcea&#8217;s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core operating segment results and Akcea recognizes the fees as R&amp;D expense. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our condensed consolidated balance sheet.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617384" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617385">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617385" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617386"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_2958b39c1bf14cc1be4632f290a898e3" contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" escape="true" continuedAt="Text_4a02e0a117b744748b70e109f71829681">
<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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617386" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617387"><ix:continuation id="Text_4a02e0a117b744748b70e109f71829681" continuedAt="Text_4a02e0a117b744748b70e109f71829682">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617387" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617388"><ix:continuation id="Text_4a02e0a117b744748b70e109f71829682">
<table cellpadding="0" cellspacing="0" id="zd0e86e09a7c74df9a1e6577ab1ae4307" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></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;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_3e0980aa73dc4edeada62e83786fc5ae" contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">8.5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0fe401e466654d9cab7b60d1d2dc3b68" contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.2</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_50de6a612bf04e37a6a54e6af77b30c3" contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">176.3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_181b9eca967c4804bcde99ca0fe9283c" contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">42.7</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_45195fdcf03246e0b6e1bf53b6f66bf4" contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_1c18cc9598c04ddb8417166c81b0ee40" contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_52b3db77cbb04011bc85653e37a2c830" contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">28</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_61dbbb0a096542b984b1774803c875ef" contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">10</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617388" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617389">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617389" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617390">
<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 nine months of 2019, we did not have any changes to our performance obligations, except as noted above, or the timing in which we expect to recognize revenue under our Novartis collaboration.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617390" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617391">
<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_64e2dd576f1c4dc9a925f263c12d617391" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617392">
<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 September 30, 2019 and December 31, 2018 included deferred revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_99ffee2d2b3a4cf2b2e69fbc5c919abd" contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">10.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_5d3b3d7795a9467497353204dc78ce44" contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">28.8</ix:nonFraction> million, respectively, related to our relationship with Novartis.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617392" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617393">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617393" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617394">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pfizer</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617394" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617395">
<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_64e2dd576f1c4dc9a925f263c12d617395" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617396">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2019, Akcea initiated a collaboration with Pfizer for the license of AKCEA<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub> to treat people with cardiovascular and metabolic diseases. Akcea is currently conducting a Phase 2 study of AKCEA<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub> for the treatment of non-alcoholic fatty liver disease, or NAFLD. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the ongoing Phase 2 study.</div>
</ix:continuation><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617396" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617397">
<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_64e2dd576f1c4dc9a925f263c12d617397" continuedAt="Text_64e2dd576f1c4dc9a925f263c12d617398">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, Akcea will receive a $</span><ix:nonFraction name="ions:UpfrontLicenseFeeToBeReceived" id="Fact_914e1de1479a4f0fa6a731f5fa0ae4c2" contextRef="c20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">250</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront license fee, upon closing the transaction, including receiving Hart-Scott Rodino clearance. Akcea is also eligible to receive development, regulatory and sales milestone payments of up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" id="Fact_50d6ac96e23442f48d9e722ee08e4747" contextRef="c20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U002" decimals="-8" scale="9" format="ixt:numdotdecimal">1.3</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion and tiered royalties in the mid-teens to low-</span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfDrug" id="Fact_03a58f57ace24d6da586c736b9b4ee05" contextRef="c20191001to20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on annual worldwide net sales. Akcea has retained the rights to co-commercialize AKCEA</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and certain additional markets. The license fee, milestone payments and royalties will be split equally between us and Akcea. Upon receipt of the upfront payment from Pfizer</span>, Akcea expects to pay us its $<ix:nonFraction name="ions:SublicenseFeePaidForLicenseOfDrug" id="Fact_b96ff8c3b6274a80b59763786929eb14" contextRef="c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">125</ix:nonFraction> million sublicense fee in <ix:nonFraction name="ions:ReceiptOfSharesInSubsidiary" id="Fact_5c440effcc5c4f1a9b78bc4e95d26a09" contextRef="c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.9</ix:nonFraction> million shares of Akcea common stock.</div>
</ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:SegmentReportingDisclosureTextBlock" id="Text_57f65420568e45369307ebb510015484" contextRef="c20190101to20190930" escape="true" continuedAt="Text_6d86be6003124adaa9097a570a063d471">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Segment Information</div>
</ix:nonNumeric><ix:continuation id="Text_6d86be6003124adaa9097a570a063d471" continuedAt="Text_6d86be6003124adaa9097a570a063d472">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_6d86be6003124adaa9097a570a063d472" continuedAt="Text_6d86be6003124adaa9097a570a063d473">
<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 have </span><ix:nonFraction name="us-gaap:NumberOfReportableSegments" id="Fact_9dbbdc685892440db0d13157dc93e1ac" contextRef="c20190101to20190930" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> reportable segments, Ionis Core and Akcea Therapeutics. </span>At September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>we owned approximately <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_8a08cad174d343278b9affb09890ce08" contextRef="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">75</ix:nonFraction> percent of Akcea.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</span></div>
</ix:continuation><ix:continuation id="Text_6d86be6003124adaa9097a570a063d473" continuedAt="Text_6d86be6003124adaa9097a570a063d474">
<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_6d86be6003124adaa9097a570a063d474" continuedAt="Text_6d86be6003124adaa9097a570a063d475">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.</div>
</ix:continuation><ix:continuation id="Text_6d86be6003124adaa9097a570a063d475" continuedAt="Text_6d86be6003124adaa9097a570a063d476">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_6d86be6003124adaa9097a570a063d476" continuedAt="Text_6d86be6003124adaa9097a570a063d477">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea is </span>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea generates revenue from TEGSEDI and WAYLIVRA product sales and from its collaborations.</span></div>
</ix:continuation><ix:continuation id="Text_6d86be6003124adaa9097a570a063d477" continuedAt="Text_6d86be6003124adaa9097a570a063d478">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_6d86be6003124adaa9097a570a063d478" continuedAt="Text_6d86be6003124adaa9097a570a063d479"><ix:nonNumeric name="us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock" id="Text_c9763be15f2e4286b463292d699ff0e8" contextRef="c20190101to20190930" escape="true" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd1">
<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 show our segment revenue and income (loss) from operations for the three and nine months ended&#xA0;September 30, 2019 and 2018 (in thousands), respectively.</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd1" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd2"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d479" continuedAt="Text_6d86be6003124adaa9097a570a063d4710">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd2" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd3"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4710" continuedAt="Text_6d86be6003124adaa9097a570a063d4711">
<table cellpadding="0" cellspacing="0" id="z0ad30f1f4f2a4ba8890de9668d5998f8" 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;">Three Months Ended September 30, 2019</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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; 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>
    <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: top;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" 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: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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_53323a19912f41f5b876b834bbeff857" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">81,672</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5ca9c293944e4626b9c67249e8caf5c4" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9e2db1c4f3e1470a93fb35f6c30b12df" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember" 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b1ea86e8dcf041b1b04c06ed9580538e" contextRef="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">81,672</ix:nonFraction></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: 52%; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e86953f901094abb917df1ce9e7f1c5f" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5361af2359594a0ca14fe4e63abb964c" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,945</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fe0d7a4ec93e45bda279181b743970cb" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b5c41e8db8e7459e9599bf6248ece32f" contextRef="c20190701to20190930_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,945</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#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_e78f66dbeecd4134b5696fb1e56fae5e" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,946</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_cc8888b2e2ad4174a10dcde5ca08310e" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">136</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_0abeaa0269f44ffb8fdf5e7ebccfe360" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e551e001dc374020a44354b8b11c0afd" contextRef="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,082</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4d58f26f50fe4b34a3fd74381938cde6" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">83,618</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c67bc8aa4a8e44e8ad3eab68dc216d67" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,081</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1ea8d3e1655a40e4be55ea071097b4ff" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ea8fba47d62f47e4905fab1189c26de9" contextRef="c20190701to20190930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">95,699</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#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_4c1402db490b4113af507188c310049a" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">69,165</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_a6f7a37607aa4ca88f8ad9370426fb47" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">8,543</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_c7248bf6d51a487191a956373a1d9bf0" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">5,515</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fc5f98eb4c944d4293a1717df0086b82" contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">72,193</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2623a77e02d44aea8daab02a515f0fd7" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">152,783</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b0bb8fdee4064bce8555c2ca8433b6be" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">20,624</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f117373797c94dee9191fa125aec4f1f" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">5,515</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8e18850dea3e4a1da72f4ea97deea76e" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">167,892</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_c3d5334cbb20457ba631760a2c28be98" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">119,147</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_06cd5a03d71a4718bfe0f49c9a330b1a" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">53,215</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:CostsAndExpenses" id="Fact_e29f4b9d44ce436ea437fec9ab78796d" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">6,993</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_e33ca529121345a8b6ae31a41aa723ed" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">165,369</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_16991713b8214921b9185f73f0b869f0" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">33,636</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_c9e381a015c84feda7b3e08764d8e527" contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,591</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_5638d93992f74ea6b438a00ed72d78ab" contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,478</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_e3aad9d647ab485387effff6f0747a0d" contextRef="c20190701to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,523</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd3" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd4"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4711" continuedAt="Text_6d86be6003124adaa9097a570a063d4712">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>30</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd4" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd5"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4712" continuedAt="Text_6d86be6003124adaa9097a570a063d4713">
<table cellpadding="0" cellspacing="0" id="z1fe532a6dd9c40528713d7c7fce08810" 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;">Three Months Ended September 30, 2018</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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#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: top;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" 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: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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_2d84e097aaa8452a987ecd7b7ef64e2a" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">70,010</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_01256613cdd443688f89f70fce4756cb" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7826ba25f57f45efae65ed71f31bbc24" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember" 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f0ff404e2e044dd59bb2259c1ee7ad05" contextRef="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">70,010</ix:nonFraction></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: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_462efc2471ac4bb49822a87d39cc0d66" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,946</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_531983e7fc1d49468168054ab8840f6b" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,000</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4ef6d1f6d5de421292778c4c210e1e20" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,200</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e3f771dc08a84be58bf5e2c1550325fe" contextRef="c20180701to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,746</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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_026f56ce5a3e400089c37d0bb4b394d8" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">77,956</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_69febac3fe8049899394ef86b27db325" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,000</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_76994a2169b444eabba0f3cee2fd4803" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,200</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3904d9249d67416aa03f65c12b8166c7" contextRef="c20180701to20180930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">82,756</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_19340268b46749d1acf8619fa5ab56d6" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">100,105</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_86c01d862cc8479e96b53d3416c2a678" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,241</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_197b40371db441b1b8c8a68ad699f009" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">44,707</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d604786849aa4294ade4374fde2c8a36" contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">62,639</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_79b7ff155fa34efab669148836c429d2" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">178,061</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8072f6800c3f42d5870ad2f79e40be14" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,241</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_66e13b201ea04fb5aa09953de816359f" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">51,907</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_865505e750c449a582f0a048347cce9c" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">145,395</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_3c4c72c6a09547cfb7c62607e9ce0675" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">87,664</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_32bbf75a2b3e49a3b8ca531695f8c5e2" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">84,249</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_fd3a46040b484041ad1788b93720843f" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,946</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_996549b1efb842bfa681165a11e9c5a3" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">163,967</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:OperatingIncomeLoss" id="Fact_f90eb41ecadf410b914e006c3814712e" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">90,397</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_5f8bbdbf1f1845deacc26c5e02dcc7bd" contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">65,008</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:OperatingIncomeLoss" id="Fact_7ae6bebdda974d689507d7b8d1557e4d" contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">43,961</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:OperatingIncomeLoss" id="Fact_76ca5e065c58496b9fc4aad4ab5b6b50" contextRef="c20180701to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">18,572</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>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd5" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd6"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4713" continuedAt="Text_6d86be6003124adaa9097a570a063d4714">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd6" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd7"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4714" continuedAt="Text_6d86be6003124adaa9097a570a063d4715">
<table cellpadding="0" cellspacing="0" id="zc3a76d4662b34f2ea78dc5e6136dfb77" 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;">Nine Months Ended September 30, 2019</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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; 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>
    <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: top;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" 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: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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_640fcd24deab492aab126433a9ef8352" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">211,884</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0387152e55e74b63af15df208e7a370b" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9e176794a7b749849a2083f3f1bfef5a" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember" 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7977f9ee2daf4f2c9a39c2838b5553e6" contextRef="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">211,884</ix:nonFraction></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: 52%; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ed4d10d33ef14e4ab59273bf3fb6306c" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c722e9964b5643daa95aebf142f71560" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">28,563</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d8acd965f2c7499182c997da7e03ba16" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember" 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: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_69c3c61419bf437eb6eb78ef1954f3d3" contextRef="c20190101to20190930_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">28,563</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#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_9bdaf2f2f59842ddad44e83a56d6b97a" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">8,466</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_12d23620e6d64f7e9a6665138998e516" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,172</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#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_8ca0270f0b1d4ff0853035da41cc532f" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,000</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5eba0150505e4f55ba65e72325562287" contextRef="c20190101to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,638</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_14d3ac6051474c57b4044a9e3c25dc5f" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">220,350</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_157a939271cd4662beddcbbf1f1ffab2" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,735</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_06899842b21349a89885c3510ac18e2a" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,000</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ceef1111917b4b4a9a57e31726e8a138" contextRef="c20190101to20190930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">252,085</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#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_364b1bc2ef1f44edbb8d33552c9a6b2e" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">294,512</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_57078f844c84488597a9c42691c14792" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">176,328</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_846a00142e7c4fbbb69f8ddddfa1d195" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">94,007</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#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_7455062d26394bb984474d050ef9cb68" contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">376,833</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_466c1123e4fe4ec6987969e0a983142e" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">514,862</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_516791355aa14815ac8ebd7b1fbaa749" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">211,063</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0af4398850084064aa910459b3b4b314" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">97,007</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_faaa59c4dce74ab69b467855f90a5daa" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">628,918</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_2477b75f32d741b690b2159a58975f6c" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">355,437</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_c00c18f9087a46979e3ec82f85e108f2" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">256,152</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:CostsAndExpenses" id="Fact_e46418be4e0043239214b189774788cd" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">87,900</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_af391b005edc467c8376dac5e4c4d1bb" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">523,689</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_7fb6c0d939b847d89e201679f680390b" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">159,425</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_a9d58f5f33084b85a44e3b4857953f89" contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">45,089</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_8e0e875287004df7a4873512ac7d3829" contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">9,107</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_b062096c1aa14a4c816b2464b77ace26" contextRef="c20190101to20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">105,229</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd7" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd8"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4715" continuedAt="Text_6d86be6003124adaa9097a570a063d4716">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd8" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd9"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4716" continuedAt="Text_6d86be6003124adaa9097a570a063d4717">
<table cellpadding="0" cellspacing="0" id="zcf2b13dc1bb64910b74499773f3efba3" 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;">Nine Months Ended September 30, 2018</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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#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: top;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" 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: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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_04e06da9c3be457b93e3f21714719d0c" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">167,743</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fdaaf16de0e241abbe360e67e9872c24" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_324b047595da4acdbf620de786c48c7d" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember" 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7fb1f23159c74407bc90a22aecd4e1f2" contextRef="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">167,743</ix:nonFraction></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: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2cd414e0a5f246e08e5c16019fc6edd8" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,432</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b20440321a31424ca56f6e02b58c78b9" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,000</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b6462f0156254f148056dd9585907bab" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,200</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5a72ada2f2774b4c836d96a696659386" contextRef="c20180101to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,232</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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_afc55777a60b40b8ab2675e014f4f7f9" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">177,175</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>
    <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_893bcf86d8af4010b8b5b5625efd3825" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,000</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_9790328f1cae47cbb22831987fadf1ed" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,200</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_13dfdcb4903d438ab46f02c4643a0e0a" contextRef="c20180101to20180930_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">181,975</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2bf9058c58da475d9caffd1182cb7887" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">232,850</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0562374ab6c84fd99338737c88e29283" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">42,670</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_af31e747523849f79c6fa2575c909c6b" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">49,936</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_37db24a2d53c479db81ad2e54f057dd6" contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">225,584</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c739d545f46840f0a6054d46e77ca859" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">410,025</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4cf45017bd1e45ea9b5a64d162bb6904" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">54,670</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3b0ded8164864ba88a14929cdf2f382f" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">57,136</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ded482ce48c4445794a4185228731868" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">407,559</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_2d96460f21d94905a83624cb023a3c3f" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">279,084</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_805b13df07d94a4b94d66ee7e338e924" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">213,428</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_98ce477691184e1b960a1fea451e4560" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">12,796</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_5a9a86233bf44c7b99d0d2473f15fa8f" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">479,716</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:OperatingIncomeLoss" id="Fact_20a20d1c63f240609a8add7169741e07" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">130,941</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_24e4ceca8f6c403e887f6e1c0a9ea9c4" contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">158,758</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:OperatingIncomeLoss" id="Fact_cd9ab2269af44131898565bf9139fcc7" contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">44,340</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:OperatingIncomeLoss" id="Fact_75f9aed8281f40488f8b98dfb0b42f91" contextRef="c20180101to20180930" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">72,157</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>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd9" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd10"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4717" continuedAt="Text_6d86be6003124adaa9097a570a063d4718">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd10" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd11"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4718" continuedAt="Text_6d86be6003124adaa9097a570a063d4719">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table shows our total assets by segment at September 30, 2019 and December 31, 2018 (in thousands), respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd11" continuedAt="Text_79e9830b97684ce99c1c76c916ef54cd12"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4719" continuedAt="Text_6d86be6003124adaa9097a570a063d4720">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_79e9830b97684ce99c1c76c916ef54cd12"><ix:continuation id="Text_6d86be6003124adaa9097a570a063d4720">
<table cellpadding="0" cellspacing="0" id="z6c5c599a255e4059847439344a157872" 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;">Total Assets</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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</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;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">September 30, 2019</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:Assets" id="Fact_c3a5810a7f784135902bba47ba0b155d" contextRef="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,233,175</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_fa83731928db429989893cb80f73b1d6" contextRef="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">383,167</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:Assets" id="Fact_873771d081084385a5b4d5d09eaf5746" contextRef="c20190930_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">721,353</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_4208e1cc956a42b5920991c0c42909bd" contextRef="c20190930" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,894,989</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2018</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_ab44db8a535a4a40ae1895ff99b64614" contextRef="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,975,491</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_efaf7ebcb4eb4b7da50d13fc3b7ed6b1" contextRef="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">365,261</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:Assets" id="Fact_acec55974f0141ff85cd77b37d1732d8" contextRef="c20181231_ConsolidationItemsAxis_IntersegmentEliminationMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">672,968</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Assets" id="Fact_270e73cd1d254acf8d16d0b0155bd3e8" contextRef="c20181231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,667,784</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>31</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z01f5aa500676401bb04174cb6d9c5a82">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 2.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</div></td>
  </tr>
</table>
</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;">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 majority 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) and our technologies and products in development, including the business of Akcea Therapeutics, Inc., our majority-owned affiliate. 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, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. 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, 2018, 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;">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 discovering and developing RNA-targeted therapeutics with sustained and growing revenues. We have created an efficient and broadly applicable drug discovery platform leveraging our expertise in antisense oligonucleotide therapeutics that we believe has fundamentally changed medicine and transformed the lives of people with devastating and often deadly diseases. Our large, diverse and advanced pipeline of over 40 first-in-class and/or best-in-class medicines addresses diseases across a broad range of therapeutic areas, targeting small, medium and large patient populations.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have three commercial medicines approved in major markets around the world, SPINRAZA, TEGSEDI and WAYLIVRA. We have two medicines in Phase 3 studies, IONIS-HTT<sub>Rx</sub>,<sub>&#xA0;</sub>for Huntington&#8217;s disease, and tofersen<sub>, </sub>for SOD1-ALS. We also have the potential for two more medicines to begin Phase 3 studies this year and additional medicines to begin Phase 3 studies by the end of 2020. These medicines, along with the more than 30 additional medicines in our pipeline, represent multiple potential drivers of value for years to come. We believe our efficient drug discovery platform, coupled with our innovation-centric business model, provides us with the flexibility to determine the optimal development and commercialization strategy to maximize the commercial opportunity for each of our medicines and ensure that we continue to produce transformative medicines for patients who need them. We believe we are positioned to drive substantial 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;">As of September 2019, SPINRAZA was approved in over 50 countries around the world, and our partner Biogen, who is responsible for global SPINRAZA commercial activities, reported that more than 9,300 patients were on SPINRAZA therapy. SPINRAZA was the first approved medicine for the treatment of SMA. SPINRAZA is the established foundation-of-care for patients of all ages and all SMA types with this progressive, debilitating and often fatal genetic disease. SPINRAZA has been recognized with several Prix Galien awards. Through September 30, 2019, we have earned more than $560 million in commercial revenues from 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, a once weekly, self-administered subcutaneous medicine, was approved in 2018 in the U.S., EU and Canada for the treatment of polyneuropathy caused by hATTR in adult patients. hATTR is a debilitating, progressive, and fatal disease. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea, our majority-owned affiliate focused on developing and commercializing medicines to treat patients with rare and serious diseases, </span>launched TEGSEDI in the U.S. and EU in late 2018. Our aim is to make TEGSEDI available globally. We plan to achieve this in part through Akcea&#8217;s exclusive license agreement with PTC to commercialize TEGSEDI in Latin America. In October 2019, TEGSEDI was approved in Brazil. PTC announced that it intends to start launching activities for TEGSEDI immediately in Brazil. In conjunction with the approval, we earned $4 million from PTC. We have earned more than $30 million in TEGSEDI product sales since launching late last year.</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;">WAYLIVRA, a self-administered, </span>subcutaneous medicine,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> received conditional marketing authorization in May 2019 from the European Commission, or EC, as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for pancreatitis. Akcea launched WAYLIVRA in the EU in the third quarter of 2019 and is also focused on regulatory discussions in the U.S. and Canada. Akcea is leveraging its existing commercial infrastructure in Europe to market WAYLIVRA. </span>Akcea is continuing to conduct open-label extension and early access programs.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We and Akcea also conducted a study of WAYLIVRA for the treatment of people with familial partial lipodystrophy, or FPL. This study is called the BROADEN study. People with FPL lack subcutaneous adipose tissue and have abnormal subcutaneous fat distribution causing increased incidence of potentially life-threatening pancreatitis, diabetes, extreme insulin resistance and increased liver fat. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2019, we and Akcea announced topline results from the BROADEN study. In the study, WAYLIVRA met its primary endpoint demonstrating </span>a statistically significant reduction in triglyceride levels. WAYLIVRA also met an important secondary endpoint with a statistically significant reduction in liver fat. Additionally, WAYLIVRA demonstrated a good safety and tolerability profile in patients with FPL in the BROADEN study. We and Akcea are continuing to evaluate the data from this study and are assessing next steps.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>32</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition to commercializing TEGSEDI and WAYLIVRA, Akcea has four other clinical-stage medicines in its pipeline: AKCEA-APO(a)-L</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(TQJ230), AKCEA-ANGPTL3-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, AKCEA-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">AKCEA-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">each of which could potentially treat multiple patient populations. Moving these medicines into Akcea ensures our core focus remains on innovation while enabling us to retain substantial value from these medicines.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> As of September 2019, we owned approximately 75 percent of Akcea.</span></div>
<div><br /></div>
<div><ix:continuation id="Text_64e2dd576f1c4dc9a925f263c12d617398">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In October 2019, Akcea initiated a collaboration with Pfizer for the license of AKCEA</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to treat people with cardiovascular and metabolic diseases. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, Akcea will receive a $</span>250<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront license fee, upon closing the transaction, including receiving Hart-Scott Rodino clearance. </span>Akcea is also eligible to receive development, regulatory and sales milestone payments of up to $1.3 billion and tiered royalties<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the mid-teens to low-20 percent range </span>on annual worldwide net sales. Akcea will pay us 50 percent of the license fee, milestone payments and royalties. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the ongoing Phase 2 study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Upon receipt of the upfront payment from Pfizer</span>, Akcea expects to pay us its $125 million sublicense fee in 6.9 million shares of Akcea common stock.</div>
</ix:continuation></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are continuously advancing our technology and pipeline to provide the most value to patients. We have a pipeline of over 40 medicines that, like SPINRAZA, TEGSEDI and WAYLIVRA, have the potential to transform the treatment of diseases with no adequate treatment today. These medicines range from treatments for rare diseases with small patient populations to more common diseases afflicting millions of patients. Our pipeline covers a broad spectrum of therapeutic areas, such as cardiometabolic diseases, neurodegenerative diseases, cancer, severe and rare diseases and others. We believe our large and diverse pipeline contains many near-, mid- and longer-term growth drivers for the company.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have a distinct partnering strategy based on each specific medicine and the expertise and resources we and our potential partners may bring to a collaboration. We may also develop and commercialize some medicines through affiliates. In general, these are medicines, like TEGSEDI and WAYLIVRA, that can benefit from our internal expertise and infrastructure, have manageable development plans and costs, and have the potential for initial rare disease indications. For other medicines, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we may establish collaborations to advance the medicine. We have alliances with a cadre of leading global pharmaceutical companies that are working alongside us in developing our medicines, advancing our technology, preparing to commercialize our medicines and selling our medicines. Our partners include the following companies, among others: AstraZeneca, Bayer, Biogen, GSK, Janssen, Novartis, Pfizer and Roche. Our partners bring resources and expertise that augment and build upon our internal capabilities.</span>&#xA0;We have the potential to earn over $20 billion in future milestone payments and licensing fees from our existing partnerships.</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 thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="za2418dbacf164beab7f0e6edf392eeed" 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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</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="6" valign="bottom" style="vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended</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; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>
    <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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; 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;">167,892</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">145,395</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">628,918</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">407,559</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #FFFFFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165,369</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">163,967</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">523,689</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479,716</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,523</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18,572</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">105,229</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(72,157</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #FFFFFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,432</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(20,365</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">99,304</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(87,747</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,163</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,559</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">109,730</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">(46,335</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>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our revenue for the first nine months of 2019 increased more than 50 percent, compared to the same period in 2018, primarily due to a more than 25 percent increase in commercial revenue from SPINRAZA royalties and increasing R&amp;D revenues including the $150 million license fee we earned from Novartis when it licensed AKCEA-APO(a)-L<sub>Rx</sub>.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses for the first nine months of 2019 increased, compared to the same period in 2018, principally due to our investments in the global launches of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI and WAYLIVRA</span>.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the first nine months of 2019 we received more than $480 million in payments from our partners, including $230 million from Biogen, $156 million from Novartis, $36 million from Roche and $22 million from Alnylam. This is compared to more than $1.3 billion received in the first nine months of 2018, which included $1 billion from Biogen for our 2018 strategic neurology collaboration. Already in the fourth quarter of 2019, we have generated $260 million in payments from Pfizer and Bayer. We believe our strong financial position should enable us to continue to execute on our corporate goals throughout 2019 and beyond.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>33</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Recent Business Highlights</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"> (Q3 2019 and subsequent activities)</span></div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z54dc5e2898dc471aa8923e5e02c64a40">
  <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;">SPINRAZA &#8211; global foundation-of-care for the treatment of patients of all ages with spinal muscular atrophy (SMA)</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3c0b879fa0d947b091844f13e4f4c43a">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Worldwide sales of SPINRAZA in the first nine months of 2019 increased by nearly 25 percent to over $1.5 billion compared to last year.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z06538dc97450477683c9749e11a59b67">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patients on SPINRAZA treatment increased by approximately 11 percent compared to last quarter to approximately 9,300 patients across global commercial, clinical and expanded access settings.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbc1a152bbed5427dabfc0a5badbd2d84">
  <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;"><span style="background-color: #FFFFFF;">o</span></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 initiate the Phase 2/3 DEVOTE study evaluating the safety and potential to achieve increased efficacy with a higher dose of SPINRAZA in SMA patients of all ages, including adults.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za1bfbf2c3ab04091b02366d7a7dc117e">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen presented new long-term follow up data from NURTURE and SHINE adding to the body of evidence underscoring SPINRAZA&#8217;s durable efficacy and established safety profile across a broad range of SMA patients.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z8a2f302f57f04217ab8d3a1ec8ce0371">
  <tr>
    <td style="width: 72pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9726;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NURTURE: Data from pre-symptomatic infants treated for up to nearly four years demonstrating consistent safety and unprecedented motor milestone achievement compared to natural history were published online in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Neuromuscular Disorders</span></div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zeca6e1b71be54be6b76d21ce2c5f6502">
  <tr>
    <td style="width: 72pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9726;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SHINE: Data demonstrating continuing improvement or stabilization in one or more measures of motor function in patients with later-onset SMA treated with SPINRAZA for up to nearly six years were presented at the annual Congress of the European Pediatric Neurology Society</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za4a6101ffb4242e8bde356f9d28b8b43">
  <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 &#8211; launched in multiple markets for the treatment of polyneuropathy of hereditary transthyretin amyloidosis (hATTR) in adult patients</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za9330005e2f1402385339e120251c400">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Approved in Brazil and p</span>reparing to launch through PTC Therapeutics</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z13a61a1a9aab4695aa3b61188e309199">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">First commercial patients treated in the United Kingdom following acceptance&#160; by the National Institute for Health and Care Excellence, or NICE, and the </span>Scottish Medicines Consortium, or SMC</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z670dfbbeabeb4787b2581b031997568f">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF;">Successfully completed pricing negotiations in Germany </span></div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z8eb631b6c9de4ebc9d348fcb85eee84e">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF;">Launched in Sweden and Austria following successful completion of reimbursement negotiations</span></div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze23f44d24b294cd0826d0ead043fa453">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preparing to launch in additional EU countries<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div></td>
  </tr>
</table>
</div>
<br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0ddcb69b57114b16b92fcdd06d970a84">
  <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;">WAYLIVRA &#8211; launched in the EU for the treatment of adults with genetically confirmed familial chylomicronemia syndrome (FCS) at high risk for pancreatitis</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z09c93eec53bd437c8654fbcb6ad5978a">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">First commercial patients treated in </span>Germany, and a reimbursed early access program (ATU) launched in France</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zfb61914b543c4480b868133c4134c982">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preparing to launch in additional EU countries</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z42972da9bbf4474fa73f056e02e92b2c">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Published results from Phase 3 APPROACH study in patients with FCS in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The New England Journal of Medicine, or NEJM</span></div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z810d6b1565b845beb8d4b3168cef25c6">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Reported top-line results from the BROADEN study of WAYLIVRA in patients with FPL, which met the primary endpoint and a key secondary endpoint</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div></td>
  </tr>
</table>
</div>
<br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc19a6894a6dc45919bffbdc73c6a7493">
  <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;">Biogen Collaboration &#8211; Developing robust pipeline of medicines for the treatment of neurological diseases</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5095456748b34260b5ff7a581da731c5">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dosed the first patient in a Phase 1/2 study targeting LRRK2 for the treatment of people with Parkinson&#8217;s disease.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zdba99346784340a58a97db295f2434bf">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Advanced multiple programs, with eight programs now in development.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br /></span></div></td>
  </tr>
</table>
</div>
<br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z708e8a85fff9423aabfa2ba1093e405d">
  <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 and Akcea generated $250 million when Pfizer licensed AKCEA-ANGPTL3-L<sub>Rx</sub> to treat patients with certain cardiovascular and metabolic diseases.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd5b3349bcb164f2da945e08ce8289e18">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are eligible to receive up to $1.3 billion in milestone payments plus tiered double-digit royalties on worldwide net sales.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z692c5c646c9b482b9c4ae95d8d21e85f">
  <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;"><span style="background-color: #FFFFFF;">o</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 50 percent portion of the $250 million license fee is expected to be settled in Akcea common stock, demonstrating our confidence in the future of Akcea.</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z7cfa98c0294c4c03976368097919221a">
  <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 earned a $25 million license fee from GSK to develop and commercialize our program for the treatment of people with chronic hepatitis B virus infection.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z6652c538808e4627bf9f21166afb576b">
  <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 generated $10 million from Bayer to advance IONIS-FXI-L<sub>Rx</sub> for the treatment of people with clotting disorders.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zba5aacac32f045e4955d3954a90785da">
  <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 and Akcea presented data from the Phase 1/2 study of AKCEA-TTR-L<sub>Rx</sub> in healthy volunteers demonstrating &gt;90 percent target reduction and a positive safety profile at the European ATTR Amyloidosis meeting and at the Heart Failure Society of America.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zfe7a3e8830674fd2982a40e0029d3291">
  <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 expanded enrollment in the GENERATION HD1 Phase 3 study of IONIS-HTT<sub>Rx</sub> (RG6042) in patients with Huntington&#8217;s disease, or HD.</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z1c0bf26ae6c94556873a6dddf00c7891">
  <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 initiated a Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with IgA nephropathy, the second disease indication under our collaboration with Roche to develop the medicine for complement-mediated diseases.</div></td>
  </tr>
</table>
</div>
</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>34</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Critical Accounting Policies</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 United States. As such, we make certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may significantly impact our quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with our audit committee of our board of directors. In the following paragraphs, we describe the specific risks associated with these critical accounting policies and we caution that future events rarely develop exactly as one may expect, and that best estimates may require adjustment.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The significant accounting policies, which we believe are the most critical to aid in fully understanding and evaluating our reported financial results, require the following:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z2a5945d958224013bf1598c936faf6a6">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Assessing the propriety of revenue recognition and associated deferred revenue;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z61f7e021cff04ea7a38b3448615cd788">
  <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;">Valuing premiums received under our collaborations;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z7cb1a8c4e5a44fc6a9667aa0c49e1832">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z92cd6d7435e94370aa723465087f778c">
  <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;">Accounting for income taxes.</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There have been no 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, 2018.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Results of Operations</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our revenue was as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z54747259524240b19625a4cdd6126cae" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; 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>
    <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>
    <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: -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;">81,672</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,010</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">211,884</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">167,743</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,945</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,563</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -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;">2,082</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;">12,746</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;">11,638</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;">14,232</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,699</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82,756</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252,085</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">181,975</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; 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%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,918</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,066</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">99,263</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,185</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; 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;">11,981</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,194</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64,013</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44,583</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; 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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,523</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,649</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">198,212</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64,227</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; 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;">10,771</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,730</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;">15,345</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;">24,589</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,193</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,639</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">376,833</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">225,584</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 81pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,892</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">145,395</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">628,918</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;">407,559</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;">We significantly increased both commercial and R&amp;D revenue in the first nine months of 2019, compared to the same period in 2018. Commercial revenue increased over 35 percent primarily due to increased SPINRAZA royalties and TEGSEDI product sales. We also added WAYLIVRA product sales in the third quarter of 2019.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our R&amp;D revenue substantially increased in the first nine months of 2019 compared to the same period in 2018 primarily due to the following:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zecef373987e84b9894a17468e334cfaf">
  <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;">$150 million we earned from Novartis when Novartis licensed AKCEA-APO(a)-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">;</span></div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5ade4d1b0e9d4d97b5a55865c7401512">
  <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;">$35 million we earned from Roche when Roche enrolled the first patient in the Phase 3 study of IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in patients with Huntington's disease;</span></div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z823b549f4f0c430ab919ceff710a7fa8">
  <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;">$25 million we earned from GSK when GSK licensed our HBV program; and</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zee023ed964ec4a7da948dbdd5b42ca3d">
  <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;">$20 million we earned from Alnylam when Alnylam licensed our technology to Regeneron.</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; margin-bottom: 15pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We expect to recognize revenue related Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx </sub>in the fourth quarter of 2019. We will also recognize $10 million of revenue from Bayer for advancing IONIS-FXI-L<sub>Rx</sub> in our fourth quarter.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>35</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><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;">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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z890bb0a421624a70a128574d7b7b4892" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82,667</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,512</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">243,920</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">213,114</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,569</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,518</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">256,105</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,188</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,993</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;">(7,946</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;">(87,900</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;">(12,796</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: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141,243</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">129,084</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">412,125</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">382,506</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,126</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;">34,883</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;">111,564</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;">97,210</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165,369</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">163,967</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">523,689</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479,716</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<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 operating expenses, excluding non-cash compensation expense related to equity awards, increased for both the three and nine months ended September 30, 2019, compared to the same periods last year principally due to our investment in the global launches of TEGSEDI and WAYLIVRA. Stock-based compensation expense increased in the first nine months of 2019, compared to the same period last year primarily due to the increase in the grant date fair value of Akcea stock options granted and from stock option grants made to new employees as Akcea continued to build out its organization. This increase was offset by a reversal of $19.1 million of stock-based compensation expense for three terminated executive officers in the third quarter of 2019. The stock-based compensation expense reversal related to amounts we</span> previously recognized related to these executive officers&#8217; stock option and RSU grants that were no longer going to vest.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Cost of Products Sold</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of products sold consisted of manufacturing costs, including certain fixed costs, transportation and freight, indirect overhead costs associated with the manufacturing and distribution of TEGSEDI and WAYLIVRA (beginning in the third quarter of 2019) and certain associated period costs. We do not expect our fixed costs will increase in direct correlation to TEGSEDI and WAYLIVRA product sales. Prior to the regulatory approval of TEGSEDI and WAYLIVRA, we expensed as R&amp;D expense a significant portion of the cost of producing TEGSEDI and WAYLIVRA that Akcea is using in the commercial launches. We expect cost of products sold to increase as we deplete these inventories.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of products sold by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zd3a47812efcf42f6ba5a351642f4e66e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Three Months Ended</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;">Nine Months Ended</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,275</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,247</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,435</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;">(7,256</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%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">840</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,991</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">127</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;">382</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; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total cost of products sold</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">967</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,373</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began recognizing cost of products sold in the third quarter of 2018 when TEGSEDI was approved and in the second quarter of 2019 when WAYLIVRA was approved. We previously expensed $0.2 million and $0.5 million of costs to produce the amount of TEGSEDI and WAYLIVRA we sold in the three and nine months ended&#xA0;September 30, 2019, respectively. We recognized these costs in prior periods because we incurred these costs before we obtained regulatory approval. We did not have cost of products sold in the first nine months of 2018. Akcea includes the amortization for milestone payments it made to us related to the U.S. and European approvals of TEGSEDI in its cost of products sold. Akcea is recognizing this amortization over TEGSEDI&#8217;s remaining estimated patent life. We eliminate this amortization in our consolidated results. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: 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 operations and R&amp;D support expenses.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>36</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</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 thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z83d7969b75a3456e921a6d77653548d1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">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;">80,622</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,475</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">245,013</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">243,455</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,744</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,780</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,935</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,698</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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;">104,366</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,255</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">316,948</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;">301,153</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z5921b750aaa34c47aefacac8b76e3f58" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64,197</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,452</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">190,269</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">158,860</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,983</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,068</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">135,388</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89,940</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,558</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;">(45</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;">(80,644</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,345</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: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">80,622</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,475</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">245,013</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">243,455</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,744</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;">18,780</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;">71,935</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;">57,698</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,366</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,255</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">316,948</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">301,153</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<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.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As we continue to advance our antisense technology, we are investing in our drug discovery programs to expand our and our partners&#8217; drug pipelines.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our antisense drug discovery expenses are part of our Ionis Core business segment and were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zc23fe346819547418f2266891958bbb9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">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;">16,072</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,475</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">46,397</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">41,970</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,015</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,379</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,805</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13,204</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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;">21,087</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,854</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,202</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;">55,174</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense drug discovery expenses were slightly higher for the three and nine months ended September 30, 2019, compared to the same periods in 2018, due to expenses we incurred related to advancing our research programs. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 the breakdown for medicines in Phase 3 development and/or commercialization for which we have incurred significant costs (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z40a87aba39424b1199fc4628b81db681" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">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;">2,324</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,469</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">7,429</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,919</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,044</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,373</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13,161</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,404</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other antisense development projects</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,233</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,413</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,121</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,580</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development overhead expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,557</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,648</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53,351</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,286</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">46,158</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,903</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,062</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148,189</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,391</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,434</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,743</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,922</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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;">57,549</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,337</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">177,805</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;">174,111</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 style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>37</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our development expenses decreased for the nine months ended September 30, 2019 primarily from WAYLIVRA, TEGSEDI and because Akcea has transitioned all further development of AKCEA-APO(a)-L<sub>Rx</sub> to Novartis. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our antisense drug development expenses by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z7c7b0f27283347e686472c41885783e7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,970</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,821</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">96,992</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">71,767</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13,188</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,082</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">121,070</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76,422</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
    <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>
    <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;">(75,000</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;">&#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: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46,158</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,903</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,062</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">148,189</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,391</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;">8,434</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;">34,743</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,922</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total antisense drug development expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,549</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,337</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">177,805</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,111</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the $75 million sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>. Akcea recognized the $75 million sublicense fee in its R&amp;D development expenses. We eliminated this expense in our consolidated results. We expect to receive 6.9 million shares of Akcea common stock as payment for the $125 million sublicense fee Akcea will owe us once the Pfizer license of AKCEA-ANGPTL3-L<sub>Rx</sub> closes. We expect Akcea will recognize the $125 million sublicense fee in its R&amp;D expenses in the fourth quarter of 2019. We will eliminate this expense in our consolidated results.</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 products 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 product. Although we may characterize a product 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 products based on each product&#8217;s particular needs at that time. This means we are constantly shifting resources among products. Therefore, what we spend on each product during a particular period is usually a function of what is required to keep the products progressing in clinical development, not what products 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 product to another and cannot be used to accurately predict future costs for each product. And, because we always have numerous medicines in preclinical and early stage clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the timing of the related costs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Manufacturing and Operations</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 operations function consist primarily of personnel costs, specialized chemicals for oligonucleotide manufacturing, laboratory supplies and outside services. Our manufacturing and operations function is responsible for providing drug supplies to antisense drug development, Akcea 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 operations expenses were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zec2b1426fbc94413b5edbcb2c64a1d10" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Manufacturing and operations 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;">9,582</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,085</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29,064</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">30,083</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,441</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,236</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,022</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,024</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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 operations 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;">12,023</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,321</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">36,086</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;">37,107</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 manufacturing and operations expenses by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z8a43c91261b3419fac63c62b6ac94f7d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,059</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,931</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">24,919</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">24,659</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,038</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,154</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,659</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,653</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,515</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;">&#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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,515</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,229</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: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,582</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,085</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29,064</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30,083</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,441</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,236</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;">7,022</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;">7,024</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and operations expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,023</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,321</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36,086</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,107</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>38</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">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 thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z220d8578d75848cd81761c93046f1105" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">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;">3,666</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,259</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">10,990</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">9,456</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Occupancy</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,463</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,379</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,894</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,281</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">600</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,796</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,745</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depreciation and amortization</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">389</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">315</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Insurance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">498</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,321</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,230</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; 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; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,454</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,382</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,101</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,186</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">8,811</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,012</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,491</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,213</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,897</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,731</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,364</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,548</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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;">13,708</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,743</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">40,855</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;">34,761</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support expenses were slightly higher for the three and nine months ended September 30, 2019, compared to the same period in 2018, primarily due to costs associated with the growth of our business. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our R&amp;D support expenses by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z23c6d9d1af5c4951bdd850cf528974d5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,097</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,225</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">21,961</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">20,464</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,757</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">832</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,659</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,865</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43</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;">(45</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;">(129</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;">(116</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: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,811</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,012</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,491</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,213</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,897</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,731</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;">14,364</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;">11,548</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13,708</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,743</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,855</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,761</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<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 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 selling, general and administrative expenses (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zc06ba313169f4f87acf1a499aea034a7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">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;">59,781</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52,609</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">164,122</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">139,051</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">255</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,103</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,246</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,512</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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;">60,036</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,712</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">203,368</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;">178,563</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SG&amp;A expenses <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">were higher for the three and nine months ended September 30, 2019, compared to the same periods in </span>2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,</span> principally due to the cost of commercializing <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI and WAYLIVRA. All amounts exclude non-cash compensation expense related to equity awards.</span></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>39</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our selling, general and administrative expenses by segment were as follows (in thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zfb9e9f4aafdc46cba28a7b4a72e54d9d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Ionis Core</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,470</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,060</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">53,651</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">54,254</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,311</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44,450</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110,470</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,248</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elimination of intercompany activity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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>
    <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;">(7,901</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;">&#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>
    <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;">(7,451</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: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subtotal</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59,781</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52,609</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">164,121</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,051</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">255</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;">16,103</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;">39,247</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;">39,512</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60,036</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68,712</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">203,368</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,563</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Akcea Therapeutics, Inc.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on operating expenses (in thousands) for our Akcea Therapeutics business segment:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z8c3beafe22534403918a1e53aff4780f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; 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;">Cost of products sold</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,275</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">10,246</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development and patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,983</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,068</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">135,388</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89,940</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative 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;">41,311</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44,450</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110,470</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,248</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Profit (loss) share for TEGSEDI commercialization activities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(8,889</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(29,410</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">56,680</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,518</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226,694</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,188</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,465</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,731</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29,458</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,240</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 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 Akcea Therapeutics 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;">53,215</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84,249</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">256,152</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;">213,428</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;">In the third quarter of 2018, Akcea began recognizing cost of products sold expenses after the approval of TEGSEDI.</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;">Akcea&#8217;s development and patent expenses increased for the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, compared to the same period in 2018 as a result of the one-time $75 million sublicense fee it paid to Ionis in Akcea common stock for Ionis' portion of the license fee Akcea received from Novartis in the first quarter of 2019. Excluding this one-time sublicense fee, Akcea's development expenses decreased primarily because Akcea has transitioned all further development of AKCEA-APO(a)-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to Novartis. In the fourth quarter of 2019, w</span>e expect Akcea&#8217;s development expenses to increase as a result of the one-time $125 million sublicense fee Akcea expects to pay to Ionis once the Pfizer license of AKCEA-ANGPTL3-L<sub>Rx</sub> closes. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The sublicense fees Akcea pays Ionis are eliminated in our consolidated results.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s SG&amp;A expenses increased in the three and nine months ended&#xA0;September 30, 2019 compared to the same periods in 2018, primarily due to Akcea&#8217;s commercialization of TEGSEDI and WAYLIVRA. For each period presented, we allocated a portion of Ionis&#8217; SG&amp;A expenses to Akcea for work we performed on Akcea&#8217;s behalf. We include these allocated expenses in Akcea&#8217;s SG&amp;A expenses in the table above. All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the first quarter of 2019, we began sharing profits and losses for TEGSEDI with Akcea under our TTR licensing agreement. As Akcea is the principal for all commercial activities related to the TTR License Agreement, Akcea records all activities related to TEGSEDI on a gross basis in its statement of operations based on the nature of the activity, including revenues, cost of products sold and sales and marketing expenses. Ionis&#8217; share of the net profit/loss from commercializing TEGSEDI is separately presented on Akcea&#8217;s statement of operations on the line titled &#8220;Profit (loss) share for TEGSEDI commercialization activities&#8221;. Since TEGSEDI is currently generating a loss, this represents the amount Ionis owes Akcea under the licensing agreement for its share of the net loss of TEGSEDI commercialization activities during the period. For the three and nine months ended&#xA0;September 30, 2019, our share of losses for TEGSEDI commercialization activities was $8.9 million and $29.4 million, respectively. With the launch of WAYLIVRA in the third quarter of 2019, Akcea will now pay Ionis royalties on WAYLIVRA product sales. We eliminate these amounts in our consolidated results.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All amounts exclude non-cash compensation expense related to equity awards.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Investment Income</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income for the three and nine months ended&#xA0;September 30, 2019 was $13.1 million and $39.0 million, respectively, compared to $10.0 million and $18.7 million for the same periods in 2018. The increase in investment income was primarily due to our significantly higher average cash balance during the first nine months of 2019 compared to the same period in 2018.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>40</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-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 thousands):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="za805f126cdb849eea5ce5124ef16ac6e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</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;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; 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>
    <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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash amortization of the debt discount and debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,558</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,856</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">28,140</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">26,072</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense payable in cash</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,714</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,714</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,141</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,141</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest on mortgage for primary R&amp;D and manufacturing facilities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">607</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">607</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,790</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,802</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">333</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">317</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total interest expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,002</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,282</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">35,404</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;">33,332</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; font-style: italic; font-weight: bold;">Income Tax Benefit (Expense)</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded an income tax benefit of $14.9 million and an income tax expense of $9.2 million for the three and nine months ended&#xA0;September 30, 2019, compared to income tax expense of $0.5 million and $0.8 million for the same periods in 2018, respectively. The tax benefit recorded for the three months ended September 30, 2019 varies from what we would have recorded using the U.S. federal statutory rate primarily due to a state tax benefit resulting from our combined state tax filings with Akcea, estimated R&amp;D and orphan drug credits, excess tax benefits related to share-based compensation and a benefit related to a change in the estimated tax value of Akcea shares we received in 2018. The increase in our income tax expense for the nine months ended&#xA0;September 30, 2019, compared to the same period in 2018, was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019. We expect to utilize our deferred tax assets to partially offset our U.S. federal taxable income.</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 Income (Loss)</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had a net loss of $18.4 million and net income of $99.3 million for the three and nine months ended&#xA0;September 30, 2019, respectively, compared to a net loss of $20.4 million and $87.7 million for the same periods in 2018. Our net income was primarily due to increased revenue year-over-year.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Loss Attributable to Noncontrolling Interest in Akcea Therapeutics, Inc.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2019, we owned approximately 75 percent of Akcea. The shares of Akcea that third parties own represent an interest in Akcea's equity that we do not control. However, because we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea's common stock in a separate line called &#8220;Net loss attributable to noncontrolling interest in Akcea&#8221; on our statement of operations. Our noncontrolling interest in Akcea on our statement of operations for the three and nine months ended&#xA0;September 30, 2019, was a loss of $7.7 million and $10.4 million, respectively, compared to $15.8 million and $41.4 million for the same periods in 2018.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Income (Loss) Attributable to Ionis Pharmaceuticals, Inc. Common Stockholders<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Net Income (Loss) per Share</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had net income attributable to our common stockholders&#8217; of $26.2 million for the three months ended September 30, 2019, compared to a net loss attributable to our common stockholders&#8217; of $4.6 million for the same period in 2018. For the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>we reported net income attributable to our common stockholders of $109.7 million, compared to a net loss attributable to our common stockholders of $46.3 million for the same period in 2018. The increase was primarily due to increases in revenue.</div>
<div><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 September 30, 2019, basic and diluted net loss per share were $0.19 and $0.18, respectively, compared to $0.03 for the same period in 2018. For the nine months ended&#xA0;September 30, 2019, basic and diluted net income per share were $0.81 and $0.79, respectively, compared to $0.33 for the same period in 2018.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liquidity and Capital Resources</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have financed our operations primarily from research and development collaborative agreements. We also finance our operations from commercial revenue from SPINRAZA royalties and product sales. From our inception through September 30, 2019, we have earned approximately $3.8 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 September 30, 2019, we have raised net proceeds of approximately $1.8 billion from the sale of our equity securities, not including the $182.4 million Akcea received in net proceeds from its IPO in July 2017. Additionally, we have borrowed approximately $1.4 billion under long-term debt arrangements to finance a portion of our operations over the same time period.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>41</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2019, we had cash, cash equivalents and short-term investments of $2.2 billion and stockholders&#8217; equity of $1.5 billion. In comparison, we had cash, cash equivalents and short-term investments of $2.1 billion and stockholders&#8217; equity of $1.2 billion at December 31, 2018. Our cash, cash equivalents and short-term investments increased in the first nine months of 2019 primarily from payments we received from Biogen, Novartis and Roche. We expect to receive $260 million in payments we generated from Pfizer and Bayer so far in the fourth quarter of 2019.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In September 2019, our board of directors approved an initial share repurchase program of up to $125 million of our common stock. Our stock repurchase program has no expiration date. To date, we have not repurchased any shares of our common stock. We plan to make stock repurchases under this program over time in open market transactions. </span>We may consider additional share repurchases in the future as part of our overall capital allocation strategy.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At September 30, 2019, we had consolidated working capital of $2.2 billion compared to $1.9 billion at December 31, 2018. As of September 30, 2019, our debt and other obligations totaled $763.4 million compared to $763.9 million at December 31, 2018. The increase in our debt and other obligations is from the operating lease liability we added to our balance sheet when we adopted the new accounting guidance for leases on January 1, 2019.</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 September 30, 2019. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt in the paragraphs following the table:</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z6447c228b98442719686369e2c49d424" 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: -10pt; margin-left: 10pt; 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="18" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Payments Due by Period (in millions)</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; 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;">1-3 years</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;">3-5 years</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;">After 5 years</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: 40%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible senior notes (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">702.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">695.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 40%; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building mortgage payments</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 40%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1.0</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.1</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 40%; padding-bottom: 2px; background-color: #FFFFFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating leases</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 40%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">806.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">706.6</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">75.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our contractual obligations consist primarily of our convertible debt. In addition, we also have facility mortgages, facility leases 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.</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;">1 Percent Convertible Senior Notes</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In November 2014, we completed a $500 million offering of convertible senior notes, which mature in 2021 and bear interest at 1 percent. </span>We used a substantial portion of the net proceeds from the issuance of the 1 percent convertible senior notes to repurchase $140 million in principal of our 2&#190; percent convertible senior notes. As a result, the principal balance of the 2&#190; percent notes following the repurchase in November 2014 was $61.2 million.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2016, we issued an additional $185.5 million of 1 percent convertible senior notes in exchange for the redemption of $61.1 million of our 2&#190; percent convertible senior notes. At September 30, 2019, we had a nominal amount of our 2&#190; percent convertible senior notes outstanding. At September 30, 2019, we had the following 1 percent convertible senior notes outstanding (amounts in millions except price per share data):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z204fe463a9994363a2bcc9e75b10c865" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1 Percent Convertible</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Senior Notes</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">685.5</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: top; background-color: #FFFFFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Original issue date ($500 million of principal)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">November 2014</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; 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;">Additional issue date ($185.5 million of principal)</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;">December 2016</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; background-color: #FFFFFF;"><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: #FFFFFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #FFFFFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">November 2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #FFFFFF;"><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%; background-color: #FFFFFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.81</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3</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>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest is payable semi-annually. The notes are convertible under certain conditions, at the option of the note holders. We settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the 1 percent notes prior to maturity, and no sinking fund is provided for them. Holders of the 1 percent notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indenture governing the 1 percent notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus accrued and unpaid interest.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>42</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Financing Arrangement</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2015, we entered into a five-year revolving line of credit agreement with Morgan Stanley Private Bank, National Association, or Morgan Stanley, which we amended in February 2016. Under the amended credit agreement, Morgan Stanley provided a maximum of $30 million of revolving credit for general working capital purposes. During the third quarter of 2019, we paid off our total outstanding borrowings of $12.5 million under the agreement and subsequently terminated the agreement.</div>
<div><br /></div>
<div style="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. We purchased our manufacturing facility in July 2017 for $14.0 million. We financed the purchase of our primary R&amp;D facility and manufacturing facility, with mortgage debt of $51.3 million and $9.1 million, respectively. 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 September 30, 2019 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 plan to continue to enter into collaborations with partners to provide for additional revenue to us and we may incur additional cash expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other financing alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, or securing lines of credit. Whether we use our existing capital resources or choose to obtain financing will depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z360c0222671445fdadc6f73b03961304">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 3.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</div></td>
  </tr>
</table>
</div>
</div>
<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 long-term debt arrangements and, secondarily, 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, commodity prices, equity prices or other market changes that affect market risk sensitive instruments.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are also exposed to changes in foreign currency exchange rates as we have foreign subsidiaries with functional currencies other than the U.S. dollar. </span>We translate our subsidiaries&#8217; functional currencies into our reporting currency, the U.S. dollar. As a result, our financial position, results of operations and cash flows can be affected by market fluctuations in the foreign currencies to U.S. dollar exchange rate,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>which are difficult to predict. A hypothetical 10 percent change in foreign exchange rates during any of the periods presented would not have had a material impact on our consolidated financial statements. Our business strategy incorporates potentially significant international expansion, particularly related to TEGSEDI and WAYLIVRA, therefore we expect that the impact of foreign currency exchange rate fluctuations may become more substantial in the future.</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9831a60bca0842489f281f4e7f08a89e">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONTROLS AND PROCEDURES</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We maintain disclosure controls and procedures 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 September 30, 2019. There have been no significant changes in our internal controls or in other factors that could significantly affect internal controls subsequent to September 30, 2019.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>43</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">PART II &#8212; OTHER INFORMATION</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbdf38bb9ced440949204d142a6c57e5e">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 1.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LEGAL PROCEEDINGS</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z004f30bc655a443a98133a53cee47b5c">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">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>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Investing in our securities involves a high degree of risk. You should consider carefully the following information about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment. 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, 2018.</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 Ionis Core and Akcea Therapeutics Businesses</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, we are not likely to generate 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, including SPINRAZA, TEGSEDI and WAYLIVRA, our success will depend upon the medical community, patients and third-party payors accepting our medicines as medically useful, cost-effective and safe. Even when the FDA or foreign regulatory authorities authorize our or our partners&#8217; medicines for commercialization, doctors may not prescribe our medicines to treat patients. We and our partners may not successfully commercialize additional medicines.</div>
<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 may sell our medicines in the future, if we cannot agree with the government 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 payors could decrease the price received for our medicines or increase patient coinsurance to a level that makes our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, unaffordable.</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, depends upon a number of factors, including the:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z081a5cd7e18f4c0f876b7b59063a3e7e">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z116e80eb96074cd59c36c201938a1d43">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z15fde4db4d2146b3bc0b032dac18f69d">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zba1c8518dc564a03bc87b423e3f74faf">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9d92eb5ed7e14df798a1d97b818e6abb">
  <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 payors.</div></td>
  </tr>
</table>
</div>
</div>
<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, payors or the medical community in general may not accept and/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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, the product label for TEGSEDI in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis, requires periodic blood and urine monitoring, and TEGSEDI has a Risk Evaluation and Mitigation Strategy, or REMS, program. </span>Our main competition in the U.S. market for TEGSEDI is ONPATTRO (patisiran), marketed by Alnylam Pharmaceuticals, Inc. Although ONPATTRO requires intravenous administration and pre-treatment with steroids, it does not have a boxed warning or REMS. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, in the clinical studies with WAYLIVRA, declines in platelet counts were observed in many patients and some patients discontinued the studies because of platelet declines. The product label for WAYLIVRA requires periodic blood monitoring. In each case, these label requirements could negatively affect our ability to attract and retain patients for these medicines. We believe that the enhanced monitoring we have implemented to support early detection and management of these issues can help manage these safety issues so that patients can continue treatment. Since implementation of the enhanced monitoring, serious platelet events have been infrequent. While we believe we and Akcea can better maintain patients on TEGSEDI and WAYLIVRA through patient-centric commercial approaches where we plan to have greater involvement with physicians and patients, if we cannot effectively maintain patients on TEGSEDI or WAYLIVRA, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</span></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>44</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; 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, will not contribute significant revenues.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and specialized biopharmaceutical firms. Other companies engage in developing antisense technology. Our competitors may succeed in developing medicines that are:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z001a8a5d018c4a3e989933a4d0dc8f54">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z91ebd740a47741bb8484a5294227bad1">
  <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 payors than our medicines;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z10b696c3857f44508870330591a42adb">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zebe1132c7c4342b6acebb69f05719df9">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z061dc0a06ef8429da8c9749e83c1167f">
  <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>
</div>
<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, 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. Marketing and sales capability is another factor relevant to the competitive position of our medicines, and we will primarily rely on our partners and Akcea to provide this capability.</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 of products against targets that are also targets of products in our development pipeline. For example, ZOLGENSMA (approved in the U.S. for the treatment of pediatric patients less than two years of age with SMA), risdiplam (RG7916), reldesemtiv and firdapse could compete with SPINRAZA, and ONPATTRO (approved in the U.S. and Europe for a similar indication as TEGSEDI), VYNDAQEL and VYNDAMAX (approved in the U.S. for patients with both hereditary and wild type ATTR cardiomyopathy and in the EU for stage 1 hATTR amyloidosis with polyneuropathy), AG10, CRX-1008 and vutrisiran could compete with TEGSEDI. Also, metreleptin and gemcabene could compete with WAYLIVRA, while laquinimod, OMS823, selistat, VX15, WVE-120101 and WVE-120102 could compete with IONIS-HTT<sub>Rx</sub>. Furthermore, arimoclomol could potentially compete with tofersen.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Following approval, our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA could be subject to regulatory limitations. *</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 drug products. We or our partners may not obtain the labeling claims necessary or desirable to successfully commercialize our drug products, 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;">The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved drug product through the product label and on advertising, promotional and distribution activities. For example:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze2885bb682864052982149aa51697448">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z593685be45674af1bd08a2a1e937c17e">
  <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;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb37146a065544309855522b013297a7c">
  <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 Risk Evaluation and Mitigation Strategy, or REMS, program; and</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z2b20b4a93d88403fbab31e0d143a63b7">
  <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;">WAYLIVRA will require periodic blood monitoring.</div></td>
  </tr>
</table>
</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, 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 or a foreign regulatory authority may withdraw marketing authorization or may condition continued marketing on commitments from us or our partners that may be expensive and/or 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 drug products are on the market, or if manufacturing problems occur subsequent to regulatory approval, we or our partners may lose regulatory approval, or we or our partners may need to conduct additional clinical studies and/or change the labeling of our drug products, including <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA, TEGSEDI and WAYLIVRA.</span></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>45</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: left; 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>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4dc22412403d4ef0a29c5cd58be1abba">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4ec540ff9e1d4e7fbb94e1e23a29d1d4">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze7fdf2dfa13f4b58b8d8fbcc5955798a">
  <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>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA, and 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, 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;">If Akcea cannot optimize and maintain effective marketing and sales capabilities or enter into agreements with third parties to market and sell TEGSEDI and WAYLIVRA, we may not generate significant product revenue from TEGSEDI or WAYLIVRA.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To successfully commercialize TEGSEDI and WAYLIVRA, Akcea must effectively manage its marketing, sales and distribution capabilities or make arrangements with third parties to perform these services. Akcea may not be successful in doing so. To commercialize TEGSEDI and WAYLIVRA in the initial indications Akcea is pursuing, Akcea will need to optimize and maintain a specialty sales force in each global region it expects to market TEGSEDI and WAYLIVRA, supported by case managers, reimbursement specialists, partnerships with specialty pharmacies, injection training, routine blood and urine monitoring and a medical affairs team. It will be expensive and time consuming for Akcea to maintain its own sales force and related compliance protocols to market TEGSEDI and WAYLIVRA. Akcea may never successfully optimize or manage this capability and any failure could preclude the successful commercialization of TEGSEDI and/or WAYLIVRA. Additionally, Akcea and its partners, if any, will have to compete with other companies to recruit, hire, train, manage and retain marketing and sales personnel.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea incurred expenses prior to the launch of TEGSEDI and WAYLIVRA to integrate and manage the associated marketing and sales infrastructure. If regulatory requirements or other factors cause the commercial launch of TEGSEDI or WAYLIVRA to be less successful than expected, Akcea will have incurred expenses for having invested in these capabilities prior to realizing any significant revenue from sales of TEGSEDI or WAYLIVRA. Akcea&#8217;s sales force and marketing teams may not successfully commercialize TEGSEDI or WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea may seek to further penetrate markets by expanding its sales force or through strategic partnerships with other pharmaceutical or biotechnology companies or third-party sales organizations. To the extent we and Akcea decide to rely on third parties to commercialize TEGSEDI or WAYLIVRA in a particular geographic market, such as the collaboration Akcea has with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America, we may receive less revenue than if Akcea commercialized TEGSEDI or WAYLIVRA by itself. Further we would have less control over the sales efforts of any other third parties involved in commercializing TEGSEDI or WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Even though certain members of Akcea&#8217;s management team and other employees have experience commercializing drug products, Akcea has no prior experience marketing, selling or distributing drug products, and there are significant risks involved in building and managing a commercial infrastructure. If Akcea cannot effectively build and manage its distribution, medical affairs, market access, marketing and sales infrastructure, or find a suitable third party to perform such functions, the commercial launch and sales of TEGSEDI and WAYLIVRA may be delayed, less successful or precluded. Such events may result in decreased sales and lower revenue, which could have a material adverse effect on our business, prospects, financial condition and results of operations. In September 2019, Akcea announced several changes to its senior leadership team, including the departure of its Chief Executive Officer, President, and Chief Operating Officer and the appointment of two new Board members and an interim Chief Executive Officer. These transitions could impair Akcea&#8217;s ability to manage its business.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>46</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If government or other third-party payors fail to provide adequate coverage and payment rates for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, our revenue will be limited.</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </span><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 payors. The majority of people 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 drug products 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.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payors, 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 drug products exists among third-party payors. Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. Further, we believe that future coverage and reimbursement will likely be subject to increased restrictions both in the U.S. and in international markets. For example, in the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several U.S. Congressional inquiries and proposed federal legislation designed to, among other things, reform government program reimbursement methodologies for drug products and bring more transparency to drug pricing. Third-party coverage and reimbursement for our products or medicines may not be available or adequate in either the U.S. or international markets, which would negatively affect the potential commercial success of our products, our revenue and our profits.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If Biogen cannot manufacture finished drug product for SPINRAZA or the post-launch supply of the active drug substance for SPINRAZA, SPINRAZA may not maintain commercial success.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is responsible for the long-term supply of both SPINRAZA drug substance and finished drug product. Biogen may not be able to reliably manufacture SPINRAZA drug substance and drug product to support the long-term commercialization of SPINRAZA. If Biogen cannot reliably manufacture SPINRAZA drug substance and drug product, SPINRAZA may not maintain commercial success, which will harm our ability to generate revenue.</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, we cannot guarantee that SPINRAZA, TEGSEDI and WAYLIVRA will be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to show the safety and efficacy of each of our medicines before they can be approved for sale. We 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 additional marketing authorizations for SPINRAZA, TEGSEDI or WAYLIVRA. 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, the agency will not approve the specific medicine or will require additional studies, which can be time consuming and expensive and which will delay or harm commercialization of the medicine. For example, Akcea received a CRL from the FDA and a preliminary notice of noncompliance withdrawal letter from Health Canada for WAYLIVRA. As result, Akcea may need to submit additional data to the FDA and Health Canada or conduct additional clinical studies before obtaining marketing authorization, which would be expensive and cause delays.</div>
<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;">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, we may need to abandon one or more of our drug development programs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the past, we have invested in clinical studies of medicines that have not met the primary clinical end points in their Phase 3 studies. Similar results could occur in clinical studies for our medicines, including the study of WAYLIVRA in patients with FPL, the study of IONIS-HTT<sub>Rx</sub> in patients with Huntington&#8217;s disease and the study of tofersen in adults with SOD1-ALS. If any of our medicines in clinical studies, including WAYLIVRA, IONIS-HTT<sub>Rx</sub> and tofersen do not show sufficient efficacy in patients with the targeted indication, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>47</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical studies.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in development, may not predict the results of subsequent clinical studies, including the study of WAYLIVRA in patients with FPL, the study of IONIS-HTT<sub>Rx</sub> in patients with Huntington&#8217;s disease and the study of tofersen in adults with SOD1-ALS. There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z854ad2fbb3e7466498e78f1b5bb321cf">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z1965d049d8184501a52b43c786616575">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbac16934e7e14ee6985a1b502c1e1572">
  <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 in the trial;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc3ad9defad2e47a68362ccee47359e6f">
  <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 may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zfb92355f670d4d3f8eca58cdaff20409">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zaff722d8d4e74b6fb6a20e64270623d1">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z82a81088f1dd4e899c4c0ac7798752d4">
  <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; and</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z724233380dbd430d9dca2d584f9f39ce">
  <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>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In addition, our current medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, are chemically similar to each other. As a result, a safety observation we encounter with one of our medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are developing. This could cause the FDA and other regulators to ask questions or take actions that could harm or delay our ability to develop and commercialize our medicines or increase our costs. For example, the FDA or other regulatory agencies could request, among other things, any of the following regarding one of our medicines: additional information or commitments before we can start or continue a clinical study, protocol amendments, increased safety monitoring, additional product labeling information, and post-approval commitments. Similarly, we recently completed a study of WAYLIVRA in patients with FPL and we have an ongoing open-label extension study of WAYLIVRA in patients with FCS, an ongoing open-label extension study of TEGSEDI </span>and expanded access programs for each medicine.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Adverse events or results from these studies could negatively impact our current or planned marketing approval applications for WAYLIVRA or the commercial opportunity for each product.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any failure or delay in the clinical studies, including the study of IONIS-HTT<sub>Rx</sub> in patients with Huntington&#8217;s disease and the study of tofersen in adults with SOD1-ALS, 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;">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 or our partner would need to establish large-scale commercial manufacturing capabilities either on our own or through a third-party manufacturer. We and Akcea will rely on third-party manufacturers to supply the drug substance and drug product for TEGSEDI and WAYLIVRA. In addition, as our drug development pipeline increases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. We have limited experience manufacturing pharmaceutical products of the chemical class represented by our medicines, called oligonucleotides, on a commercial scale for the systemic administration of a medicine. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our medicines, and some of these suppliers will need to increase their scale of production to meet our projected needs for commercial manufacturing. Further, we must continue to improve our manufacturing processes to allow us to reduce our drug costs. We 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 current Good Manufacturing Practices regulations and similar regulations in foreign countries, which the applicable regulatory authorities enforce through facilities inspection programs. We and our contract manufacturers may not comply or maintain compliance with Good Manufacturing Practices, or similar foreign regulations. Non-compliance could significantly delay or prevent receipt of marketing authorization for our medicines, including authorizations for SPINRAZA, TEGSEDI and WAYLIVRA, or result in enforcement action after authorization that could limit the commercial success of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>48</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; 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, INC Research Toronto, Inc. and Medpace for the clinical studies for our medicines, including TEGSEDI and WAYLIVRA. We rely heavily on these parties for successful execution of our clinical studies, but do not control many aspects of their activities. For example, the investigators are not our employees. However, we are responsible for ensuring that these third parties conduct each of our clinical studies in accordance with the general investigational plan and approved protocols for the study. Third parties may not complete activities on schedule or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. The failure of these third parties to carry out their obligations 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 authorizations for SPINRAZA, TEGSEDI and WAYLIVRA.</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-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 September 30, 2019, we had an accumulated deficit of approximately $0.9 billion and stockholders&#8217; equity of approximately $1.5 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 products or achieve or sustain future profitability.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 that provision, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the Tax Cut and Jobs Act of 2017, or the Tax Act, federal net operating losses incurred in 2018 and in future years may be carried forward indefinitely, but the deductibility of such federal net operating losses is limited. It is uncertain if and to what extent various states will conform to the newly enacted federal tax law.</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 Section 382 of the Code, and corresponding provisions of state law, if a corporation undergoes an &#8220;ownership change,&#8221; which is generally defined as a greater than 50 percent change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If an ownership change occurs and our ability to use our net operating loss carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations.</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 development 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 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. 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.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our collaborators can terminate their relationships with us under certain circumstances, many of which are outside of our control. For example, as part of a reprioritization of its pipeline and strategic review of its rare disease business, GSK declined its option on TEGSEDI and IONIS-FB-L<sub>Rx</sub>.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>49</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; 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>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z23c11fcc860744b2aab47229cd147ed9">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zeb4f80e99cc74bffbee23d16d584b73f">
  <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 authorization; and</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z10c0160f797340aeb1ff25b4467df130">
  <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>
</div>
<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, Janssen, 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, Janssen, Novartis or Roche, could determine that it is in its financial interest to:</div>
<div><br /></div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0a4db60b3641493db0d61630da8420cb">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zcad01f9d216645cd98749a86f9d006b6">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3c5e260b63d8436191888a7123d56175">
  <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>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these 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.</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 the clinic, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization. We base our estimates on present facts and a variety of assumptions. Many underlying assumptions are outside of our control. If we do not achieve milestones in accordance with our or our investors&#8217; expectations, including milestones related to SPINRAZA, TEGSEDI and WAYLIVRA, the price of our securities could decrease.</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 patents 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 and secure 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. 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; 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 sometimes need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. Patent and Trademark Office or the International Trade Commission or foreign patent authorities. Intellectual property litigation can be extremely expensive, and this expense, as well as the consequences should we not prevail, could seriously harm our business.</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 style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>50</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our drug programs will require significant additional research, development, preclinical and/or clinical testing, marketing authorization and/or commitment of significant additional resources prior to their successful commercialization. As of September 30, 2019, we had cash, cash equivalents and short-term investments equal to approximately $2.2 billion. If we do not meet our goals to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or to license our medicines and proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors, such as the following:</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z493afa021bb14363922bd30358ecaed4">
  <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;">successful commercialization for SPINRAZA, TEGSEDI and WAYLIVRA;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0b6209d90705455aa9c758e093f2c56f">
  <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;">additional marketing approvals for WAYLIVRA and TEGSEDI;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4fd71868dfa04c80a5d6acd15664734c">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines, including TEGSEDI and WAYLIVRA;</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z2cac064f25d04c57836594d800af88c8">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zcb324a24b7c84daba428197c73f72137">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb6427da52d864b7d9b8c8c0a00b9787a">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9ce63a4745e14de49a622ef7351ede34">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations; and</div></td>
  </tr>
</table>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z26bf56ed482e43bbb71a737e904078a8">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">competing technological and market developments, including the introduction by others of new therapies that address our markets.</div></td>
  </tr>
</table>
</div>
</div>
<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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If our planned 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, plans to transition from Chief Executive Officer to Executive Chairman of our Board of Directors. As Executive Chairman, Dr. Crooke will continue to be responsible for the activities of the board and will remain active in the company, providing strategic advice and continuing to participate in the scientific activities. Our board has selected Dr. Monia, who has been our Chief Operating Officer for the last year and a member of our team since our founding nearly 30 years ago, to serve as our Chief Executive Officer starting in January 2020. 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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder for you to liquidate your investment and could increase your risk of suffering a loss.*</div>
<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 September 30, 2019, the market price of our common stock ranged from $43.27 to $86.58 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, governmental regulation, marketing authorization, changes in payors&#8217; reimbursement policies, developments in patent or other proprietary rights, public concern regarding the safety of our medicines and general market conditions.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>51</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We cannot guarantee that we will repurchase shares of common stock under our stock repurchase program or that we will repurchase shares of common stock at favorable prices.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors authorized a program to repurchase up to $125 million of our common stock. We can provide no assurance that we will repurchase shares at favorable prices, if at all, as the amount and timing of share repurchases under such program are subject to capital availability and our determination that share repurchases are in the best interest of our shareholders and in compliance with all applicable laws and agreements. Our ability to repurchase shares will depend upon, among other factors, our financial condition, results of operations, cash balances and potential future capital requirements for strategic transactions. In addition, the share repurchase program could impact the trading price of our stock and increase volatility, and any announcement of a reduction in or discontinuance of repurchases by us under such program may result in a decrease in the trading price of our stock.</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. 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 drug products, 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;">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>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zfe5422a048b846758c8025765527eb57">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z62666b9203e94deabb37d63543034dd5">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0d136801fb2241b980f7c9f329583a32">
  <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>
</div>
</div>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z9bae517ded8b4ed19869eb19560aa04e">
  <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>
</div>
<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 affected.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If a natural or man-made disaster strikes our research, development or manufacturing facilities or otherwise affects our business, it could delay our progress developing and commercializing our medicines.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We manufacture 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. The facilities and the equipment we 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 our contract manufacturers may be harmed by natural or man-made disasters, including, without limitation, earthquakes, floods, fires and acts of terrorism; and if our facilities are affected by a disaster, our development and commercialization efforts would be delayed. Although we possess insurance for damage to our property and the disruption of our business from casualties, 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;">Provisions in our certificate of incorporation, other agreements 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 style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>52</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">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 10.3 million shares of our common stock upon conversion of our convertible senior notes. 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; 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 controls systems in order to allow management to report on and our Independent Registered Public Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act. As a result, we continue to incur additional expenses and divert our management&#8217;s time to comply with these regulations. In addition, if we cannot continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight Board, or PCAOB, or The Nasdaq Global Select Market. Any such action could adversely affect our financial results and the market price of our common stock.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing regulations that require our compliance. On July 21, 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted. There are significant corporate governance and executive compensation-related provisions in the Dodd-Frank Act that require the SEC to adopt, or where the SEC has adopted, additional rules and regulations in these areas such as &#8220;say on pay&#8221; and proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which may lead to additional compliance costs and impact the manner in which we operate our business.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Changes in tax laws, regulations and treaties could affect our future taxable income.</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 sales taxes in the U.S. and foreign income taxes, withholding taxes and transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations, including those relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>53</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div><br /></div>
<div style="text-align: justify; 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 in the past experienced periods of substantial turmoil and uncertainty characterized by unprecedented intervention by the U.S. federal government and the failure, bankruptcy, or sale of various financial and other institutions. It is possible that a crisis in the global credit markets, the U.S. capital markets, the financial services industry or the U.S. economy may adversely affect our business, vendors and prospects, as well as our liquidity and financial condition. More specifically, our insurance carriers and insurance policies covering all aspects of our business may become financially unstable or may not be sufficient to cover any or all of our losses and may not continue to be available to us on acceptable terms, or at all.</div>
<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 or 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. 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/or state breach notification laws and foreign law equivalents, subject us to mandatory 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/or 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, there can be no assurance that our efforts will prevent service interruptions, or identify breaches in our systems, that could adversely affect our business and operations and/or 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;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z91c85e7e50cb4d7d870359e8531e0589">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 2.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z536085945fcb4e838559124367dbb4f6">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 3.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">DEFAULT UPON SENIOR SECURITIES</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z242a29a5b4434019b400bd3b5b773dc2">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">MINE SAFETY DISCLOSURES</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd0462f66cf694fd099d621fb66b80702">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 5.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">OTHER INFORMATION</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>54</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3c9c1fff96fb47df8e57a209b29f3ed4">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 6.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">EXHIBITS</div></td>
  </tr>
</table>
</div>
</div>
<div><br /></div>
<div style="text-align: left;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z003a0832d7d14ecabf3fc694c0411af5">
  <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>
</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="zb903a6c60e7c4eaebfe9798ea3cf4a38">
  <tr>
    <td style="width: 7.77%; vertical-align: top; background-color: #FFFFFF; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div></td>
    <td style="width: 2.19%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: bottom; background-color: #FFFFFF; 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: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; 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: 2.19%; 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;">Amendment No. 1 to the Neurology III Agreement between the Registrant and Biogen MA Inc., dated August 16, 2019 (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed).</div></td>
  </tr>
  <tr>
    <td style="width: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex10_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2</a></div></td>
    <td style="width: 2.19%; 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;">Amendment #8 to the Research, Development and License Agreement between the Registrant, Glaxo Group Limited and Glaxosmithkline Intellectual Property Development Limited, dated July 29, 2019 (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed).</div></td>
  </tr>
  <tr>
    <td style="width: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex10_3.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3</a></div></td>
    <td style="width: 2.19%; 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;">Consent to Collateral Addition and Amendment to Loan Documents between the Registrant, Ionis Gazelle, LLC, Wells Fargo Bank, National Association, as Trustee for the Benefit of the Registered Holders of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, dated August 1, 2019.</div></td>
  </tr>
  <tr>
    <td style="width: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; 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: 2.19%; 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: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; 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: 2.19%; 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: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; 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: 2.19%; 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: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div></td>
    <td style="width: 2.19%; 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 September 30, 2019, 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' 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: 7.77%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.19%; 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: 7.77%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104</div></td>
    <td style="width: 2.19%; 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>
<div style="text-align: justify;">
<div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb767822bd4b94040b77ebe592cc889ef">
  <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>
</div>
<div><br /></div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>55</span></div>
</div>
<div style="page-break-after:always;"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div></div>
</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;" id="za91b93c6880741aabe6dc769feea0321">
  <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/ STANLEY T. CROOKE</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;">Chairman of the Board, President, 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;">Stanley T. Crooke, M.D., 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;">November 6, 2019</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;">Senior 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;">November 6, 2019</div></td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>56</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
         Document created using EDGARfilings PROfile 6.4.0.0
         Copyright 1995 - 2019 Broadridge -->
  </head>
<body bgcolor="#ffffff" style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;">
  <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="text-align: right;">
    <div style="font-weight: bold;">EXHIBIT 10.1</div>
  </div>
  <div> <br>
  </div>
  <div><font style="font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.&#160; SUCH EXCLUDED INFORMATION HAS BEEN MARKED WITH
      &#8220;[***]&#8221;.</font> </div>
  <div> <br>
  </div>
  <div>
    <table cellspacing="0" cellpadding="0" border="0" id="z2f67b90238e844098dd7ad0ee3f6626b" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">

        <tr>
          <td style="width: 100.00%;"><img src="image00001.jpg"></td>
        </tr>

    </table>
  </div>
  <div>
    <div><br>
    </div>
    <div>August 16, 2019</div>
    <div><br>
    </div>
    <div>Biogen MA Inc.</div>
    <div>225 Binney Street</div>
    <div>Cambridge, MA&#160; 02142</div>
    <div>Attention: Chris Henderson, VP, Neuromuscular and Movement Disorders</div>
    <div><br>
    </div>
    <div>
      <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z86bb00588b2d45f4b15ced13d52cb085" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

          <tr style="vertical-align: top;">
            <td style="width: 36pt;">&#160;</td>
            <td style="vertical-align: top; width: 36pt;">
              <div style="text-align: left;"><font style="font-weight: bold;">Re:</font></div>
            </td>
            <td style="align: left; vertical-align: top; width: auto;">
              <div style="text-align: left;"><font style="font-weight: bold;">Amendment No. 1 to the Neurology III Agreement</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div><br>
    </div>
    <div>Dear Chris:</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">Ionis and Biogen are parties to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement dated April 19, 2018 (the &#8220;<font style="font-weight: bold; font-style: italic;">Neurology


        III Agreement</font>&#8221;) between Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;) and Biogen MA Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Biogen</font>&#8221;).&#160; Any capitalized terms not
      defined in this letter agreement (the &#8220;<font style="font-weight: bold; font-style: italic;">Letter Agreement</font>&#8221;) will have the meanings set forth in the Neurology III Agreement, unless expressly specified otherwise.</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">Ionis and Biogen hereby acknowledge and agree that the Neurology III Agreement is hereby amended as follows:</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; The following new <u>Section 1.2.3(g)</u> is added to the Neurology III Agreement:</div>
    <div>&#160;</div>
    <div style="margin-left: 36pt;"><font style="font-weight: bold;">1.2.3(g).&#160; &#160; </font><font style="font-weight: bold; font-style: italic;"><u>Expanded High Interest Targets</u></font><font style="font-weight: bold;">.</font></div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze81bbf2868ba431c83c46ea45871f88c">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(i)</td>
              <td style="width: auto; vertical-align: top;">
                <div>The Parties, through the Neurology JRC, may add up to [***] gene targets to the High Interest Target List, beyond the [***]-target limit set forth in <u>Section 1.2.3(a)</u>, under this <u>Section 1.2.3(g)</u> (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Expanded High Interest Target</font>&#8221;).</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <table cellspacing="0" cellpadding="0" border="0" id="zdeccb1ea6e1e49eda566b6a7d8325d71" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">

          <tr>
            <td style="width: 100.00%;"><img src="image00002.jpg"></td>
          </tr>

      </table>
    </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="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div>
        <div>
          <div>Chris Henderson</div>
          <div>August 16, 2019</div>
          <div>Page 2 of 4</div>
        </div>
        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zaab8655317224a699aa3b4e8b8c824f3">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(ii)</td>
              <td style="width: auto; vertical-align: top;">
                <div>Before adding an Expanded High Interest Target to the High Interest Target List, the Parties must mutually agree upon and submit to the Neurology JRC for approval a research plan that meets the requirements of either <u>Section
                    1.2.3(g)(ii)(A)</u> or <u>Section 1.2.3(g)(ii)(B)</u> (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Expanded High Interest Target Plan</font>&#8221;) for each such proposed Expanded High Interest Target.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0cf4b63d90a841b687d68ce35f6580a6">

            <tr>
              <td style="width: 108pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(A)</td>
              <td style="width: auto; vertical-align: top;">
                <div>An Expanded High Interest Target Plan may consist of an initial plan to conduct limited research by the Parties that clearly defines the scope of work to be performed by each Party.&#160; Ionis and Biogen will use Commercially Reasonable
                  Efforts to conduct their respective activities under the Expanded High Interest Target Plan.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze5e1c49a486a4c4abd7f60a191ba5274">

            <tr>
              <td style="width: 108pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(B)</td>
              <td style="width: auto; vertical-align: top;">
                <div>An Expanded High Interest Target Plan may consist of a Target Sanction Plan.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zadb4b8b98b7f41ea89ccf10a6bff6a69">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(iii)</td>
              <td style="width: auto; vertical-align: top;">
                <div>The Neurology JRC will review and, in its discretion, approve the addition of a proposed Expanded High Interest Target to the High Interest Target List along with the Expanded High Interest Target Plan corresponding to such proposed
                  Expanded High Interest Target.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdf4e5a03bb3f4ddb89cb4f7812fe1e5f">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(iv)</td>
              <td style="width: auto; vertical-align: top;">
                <div>With respect to each proposed Expanded High Interest Target, if the Neurology JRC, in good faith, does not unanimously agree to (1) add such proposed Expanded High Interest Target to the High Interest Target List and (2) adopt the
                  Expanded High Interest Target Plan corresponding to such proposed Expanded High Interest Target, then the proposed Expanded High Interest Target will not be added to the High Interest Target List under this <u>Section 1.2.3(g)</u>.&#160; Such
                  gene target may be added to the High Interest Target List in accordance with <u>Section 1.2.3(b)</u> or may be pursued independently by the Parties in accordance with <u>Section 1.2.3(f)</u>.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb0c0ee61d1444c21906dfcff68afe81d">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(v)</td>
              <td style="width: auto; vertical-align: top;">
                <div>With respect to any Expanded High Interest Target Plan under <u>Section 1.2.3(g)(ii)(A)</u>, once the Parties complete all work under such plan and present the results of such research to the Neurology JRC or [***] days following
                  approval of such Expanded High Interest Target Plan by the Neurology JRC, whichever is earlier, the Neurology JRC will have [***] days within which to unanimously agree upon a Target Sanction Plan for such Expanded High Interest Target.&#160;
                  If the Neurology JRC does not unanimously agree upon a Target Sanction Plan for such Expanded High Interest Target within such [***]-day period, then the Expanded High Interest Target will be removed from the High Interest Target List.&#160;
                  Such gene target may be added to the High Interest Target List in accordance with <u>Section 1.2.3(b)</u> or may be pursued independently by the Parties in accordance with <u>Section 1.2.3(f)</u>.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div>
        <div>
          <div>Chris Henderson</div>
          <div>August 16, 2019</div>
          <div>Page 3 of 4</div>
        </div>
        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zbb180ed520604b0c9b59788b1928f029">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(vi)</td>
              <td style="width: auto; vertical-align: top;">
                <div>An Expanded High Interest Target that is approved by the Neurology JRC to add to the High Interest Target List will not be subject to the terms of <u>Section 1.2.3(a),</u>&#160;<u>Section 1.2.3(b)</u>, or <u>Section 1.2.3(d)(i)</u> of
                  this Agreement.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z217892f384094a1895464a02a69f5083">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(vii)</td>
              <td style="width: auto; vertical-align: top;">
                <div>Once approved by the Neurology JRC, an Expanded High Interest Target will become a High Interest Target for all purposes under this Agreement except as expressly set forth in this <u>Section 1.2.3(g)</u>, and the Expanded High
                  Interest Target Plan approved by the Neurology JRC for such Expanded High Interest Target will become part of the Neurological Disease Research Plan.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5c94854541264516b33ad0e694da2496">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(viii)</td>
              <td style="width: auto; vertical-align: top;">
                <div>If, on or after the [***] anniversary of the date an Expanded High Interest Target was added to the High Interest Target List, such target remains or becomes an Inactive Target, then, unless the Parties mutually agree through the
                  Neurology JRC that such Expanded High Interest Target may remain on the High Interest Target List, such Expanded High Interest Target will automatically be removed from the High Interest Target List and will no longer be an Expanded High
                  Interest Target.&#160; However, during the remainder of the Research Term, such target will remain a Neurology Target and the Parties may add such target to the High Interest Target List in accordance with <u>Section 1.2.3(b)</u> or again add
                  such target to the High Interest Target List in accordance with this <u>Section 1.2.3(g)</u>.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z09f771beed76436eaaaf241e2a4731dd">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right; font-weight: bold;">(ix)</td>
              <td style="width: auto; vertical-align: top;">
                <div>The maximum number of Expanded High Interest Targets set forth in <u>Section 1.2.3(g)(i)</u> may be increased or decreased by the Neurology JRC, and any such change will be reflected in the minutes of the meeting of the Neurology JRC
                  where such increase or decrease occurred and subsequently formalized in a letter between the Parties.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">2.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <u>Section 1.14.4(a)</u> is deleted and replaced in its entirety with the following:</div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zeb786bedb8e041d395d031d1a5c8eb6d">

            <tr>
              <td style="width: 36pt;"><br>
              </td>
              <td style="width: 72pt; vertical-align: top; align: right; font-weight: bold;">1.14.4(a).</td>
              <td style="width: auto; vertical-align: top;">
                <div>review and approve amendments to the Core Research Plan and the Neurological Disease Research Plan, as described in <u>Section 1.2.2</u> and <u>1.2.3(d)(iv)</u>, and review and approve Expanded High Interest Targets to add to the
                  High Interest Target List, as well as the Expanded High Interest Target Plans corresponding to such Expanded High Interest Targets, as described in <u>Section 1.2.3(g)</u>;</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">Except as expressly set forth in this Letter Agreement, nothing in this Letter Agreement will otherwise modify or amend any provision of the Neurology III Agreement.</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="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div>Chris Henderson</div>
      <div>August 16, 2019</div>
      <div>Page 4 of 4</div>
    </div>
    <div style="text-indent: 36pt;"> <br>
    </div>
    <div style="text-indent: 36pt;">This Letter Agreement may be executed in counterparts, each of which will be deemed an original, notwithstanding variations in format or file designation that may result from electronic transmission, storage and printing
      of copies of this Letter Agreement from separate computers or printers.&#160; Facsimile signatures and signatures transmitted via electronic mail in PDF format will be treated as original signatures.</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">If the terms of this Letter Agreement are acceptable to Biogen, please so indicate by executing a copy of this Letter Agreement and returning it to Ionis.</div>
    <div><br>
    </div>
    <div>Very truly yours,</div>
    <div><br>
    </div>
    <div><u>/s/ Brett Monia</u></div>
    <div>Brett Monia</div>
    <div>Chief Operating Officer</div>
    <div>IONIS PHARMACEUTICALS, INC.</div>
    <div><br>
    </div>
    <div style="font-weight: bold;"><u>AGREED TO AND CONFIRMED BY BIOGEN MA INC.</u>:</div>
    <div><br>
    </div>
    <div>By: <u>/s/ Chris Henderson</u></div>
    <div>Name: Chris Henderson</div>
    <div>Title:&#160;&#160; VP, Neuromuscular and Movement Disorders</div>
  </div>
  <div><br>
  </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-10.2
<SEQUENCE>3
<FILENAME>ex10_2.htm
<DESCRIPTION>EXHIBIT 10.2
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 6.4.0.0
         Copyright 1995 - 2019 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>
    <div style="text-align: right; color: #000000; font-weight: bold;">EXHIBIT 10.2</div>
  </div>
  <div><br>
  </div>
  <div>
    <div style="text-align: justify; color: rgb(0, 0, 0); font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED.&#160; SUCH
      EXCLUDED INFORMATION HAS BEEN MARKED WITH &#8220;[***]&#8221;.</div>
    <div><br>
    </div>
    <div style="color: rgb(0, 0, 0); font-weight: bold; text-align: center;"><u>AMENDMENT #8 TO THE RESEARCH, DEVELOPMENT AND LICENSE&#160;AGREEMENT</u></div>
    <div>&#160;</div>
    <div style="text-align: justify; color: rgb(0, 0, 0); text-indent: 36pt;">This <font style="font-weight: bold;">AMENDMENT #8 TO THE RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT</font> (this &#8220;<font style="font-weight: bold; font-style: italic;">Amendment


        No. 8</font>&#8221;) is entered into and made effective as of the 29<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day of July 2019 (the &#8220;<font style="font-weight: bold; font-style: italic;">Amendment No. 8 Effective
        Date</font>&#8221;) by and between <font style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</font>, a Delaware corporation, having its principal place of business at 2855 Gazelle Court, Carlsbad, CA 92010 (formerly &#8220;Isis Pharmaceuticals, Inc.&#8221;) (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;), and <font style="font-weight: bold;">GLAXO GROUP LIMITED</font>, a company existing under the laws of England and Wales, having its registered office at 980 Great West Road, Brentford
      London TW8 9GS, United Kingdom (&#8220;<font style="font-weight: bold; font-style: italic;">GGL</font>&#8221;), and <font style="font-weight: bold;">GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED,&#160; </font>a company existing under the laws of England
      and Wales, having its registered office at 980 Great West Road, Brentford London TW8 9GS, United Kingdom (&#8220;<font style="font-weight: bold; font-style: italic;">GSK IPDL</font>&#8221;). GGL and GSK IPDL are referred to together as &#8220;<font style="font-weight: bold; font-style: italic;">GSK</font>&#8221;. Ionis and GSK are each referred to herein by name or as a &#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; or, collectively, as &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>.&#8221;</div>
    <div>&#160; <br>
    </div>
    <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">RECITALS</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; color: #000000;"><font style="font-weight: bold;">WHEREAS</font>, Ionis and GGL are parties to the Research, Development and License Agreement dated March 30, 2010, as amended (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;) and (to the extent applicable) GGL has sub-licensed its rights under the Agreement to GSK IPDL; </div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; color: #000000;"><font style="font-weight: bold;">WHEREAS</font>, Ionis and GSK entered into Amendment No. 5 to the Agreement dated June 27, 2014 (the &#8220;<font style="font-weight: bold; font-style: italic;">Amendment No. 5</font>&#8221;) and Amendment No. 7 to the Agreement dated March 4, 2016 (the &#8220;<font style="font-weight: bold; font-style: italic;">Amendment No. 7</font>&#8221;) to amend certain terms of the Agreement solely with respect to the HBV
      Program, a Collaboration Program focused on hepatitis B virus;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; color: #000000;"><font style="font-weight: bold;">WHEREAS</font>, Ionis and GSK wish to agree to amend the Agreement to provide that certain Isis Product-Specific Patents will only be exclusively
      licensed and not assigned to GSK following the exercise of the Option for the HBV Program on the terms and conditions set forth herein.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; color: #000000;"><font style="font-weight: bold;">NOW, THEREFORE</font>, in consideration of the premises and mutual covenants herein contained, and for other good and valuable consideration, the
      receipt and sufficiency of which are hereby acknowledged, and solely with respect to the HBV Program, the Parties, intending to be legally bound, do hereby agree as follows:</div>
    <div>&#160;</div>
    <div style="text-align: justify; color: #000000;">Capitalized terms used but not defined herein will have the meaning ascribed to such terms in the Agreement, Amendment No. 5 and Amendment No. 7.</div>
    <div>&#160;</div>
    <div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z845209f3777e4cad8d36c12da783318d">

          <tr>
            <td style="width: 37.35pt; vertical-align: top;">
              <div style="color: #000000; font-weight: bold;">1.</div>
            </td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold; color: #000000;"><u>Definitions.</u></font><font style="font-weight: bold; color: #000000;"> &#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Non-Assignable


                  Ionis Product-Specific Patents</font><font style="color: #000000;">&#8221; means the Ionis Product-Specific Patents set forth in Appendix A to this Amendment No. </font>8<font style="color: #000000;">.</font></div>
            </td>
          </tr>

      </table>
    </div>
    <div><br>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">1</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <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;">
      <div>
        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z57c34a32fb1242beb3b5e348fc3f3e1d">

            <tr>
              <td style="width: 37.35pt; vertical-align: top; color: rgb(0, 0, 0); font-weight: bold;">2.</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div style="color: #000000;"><font style="font-weight: bold;"><u>Amendment of the Agreement.</u></font><font style="font-weight: bold;">&#160; </font>Solely with respect to the HBV Program, the Agreement is hereby amended as follows:</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
      </div>
    </div>
    <div>
      <div>
        <div>
          <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z4a4eab7420b143d2bd22234042415481" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

              <tr style="vertical-align: top;">
                <td style="width: 36pt;">&#160;</td>
                <td style="vertical-align: top; width: 27pt;">
                  <div style="text-align: justify; color: rgb(0, 0, 0);"><font style="text-align: left; color: rgb(0, 0, 0);">a.</font></div>
                </td>
                <td style="align: left; vertical-align: top; width: auto;">
                  <div style="text-align: justify; color: rgb(0, 0, 0);">The first paragraph of <u>Section 4.1.1</u> is deleted and replaced in its entirety with: &#8220;<u>Development and Commercialization License</u>. On a Collaboration
                    Program-by-Collaboration Program basis, subject to the terms and conditions of this Agreement, Ionis hereby grants to GSK (a):&#160; a worldwide, exclusive, royalty-bearing, sublicensable (in accordance with <u>Section 4.1.2</u>) license
                    under the Licensed IP (other than the Ionis Product-Specific Patents) to Manufacture, Develop, and Commercialize Licensed Compounds and Licensed Products, and (b) a worldwide, exclusive, royalty-bearing, sublicensable, perpetual,
                    irrevocable (except pursuant to <u>Section 10.1</u>) license under the Ionis Product-Specific Patents for any purpose related to the treatment of hepatitis B [***].</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z72997a5486d34fb4a777d6db2551f94b">

            <tr>
              <td style="width: 36pt;"><br>
              </td>
              <td style="width: 27pt; vertical-align: top; color: rgb(0, 0, 0); font-weight: bold;">b.</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div style="color: #000000;"><u>Section 6.2.2(b)</u> is deleted and replaced in its entirety with: &#8220;<u>Ionis Patents After Exercise of Option</u>. After GSK has obtained the applicable license under <u>Section 4.1.1</u> and following
                  review and approval of a majority of the members of the Joint Patent Committee, Ionis will assign to GSK all Ionis Product-Specific Patents that Cover Licensed Compounds, Licensed Products and/or the Collaboration Target included in such
                  Collaboration Program, excluding the Non-Assignable Ionis Product-Specific Patents which Ionis shall license to GSK pursuant to <u>Section 4.1.1</u>, and GSK will thereafter control and be responsible for all aspects of the Prosecution
                  and Maintenance of all such Ionis Product-Specific Patents (for clarity, including the Non-Assignable Ionis Product-Specific Patents) related to the treatment of hepatitis B viral infections, subject to <u>Section 6.2.4</u>.&#8221;</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z12d459e3aa1f4a238820dcd1e452f955">

            <tr>
              <td style="width: 36pt;"><br>
              </td>
              <td style="width: 27pt; vertical-align: top; color: rgb(0, 0, 0); font-weight: bold;">c.</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div style="color: #000000;"><u>Section 10.1</u> is deleted and hereby replaced in its entirety with the following: &#8220;<u>Reversion Rights</u>.&#160; Ionis may elect to continue to Develop and Commercialize any Discontinued Products that are the
                  subject of a termination (i) by GSK under <u>Section 9.2.1</u>, or (ii) by Ionis under <u>Section 9.2.2</u> or <u>Section 9.2.3</u>, by notice in writing to GSK after such termination (an &#8220;<font style="font-weight: bold; font-style: italic;">Election Notice</font>&#8221;) that Ionis is exercising its rights under this <u>Section 10.1</u>, in which case GSK will grant to Ionis a sublicensable, worldwide, exclusive license or sublicense, as the case may be, to all GSK
                  Technology Controlled by GSK as of the date of the Election Notice solely as they are necessary to make, have made, use, sell, offer for sale, have sold and import Discontinued Products. Such license will be sublicensable by Ionis in
                  accordance with <u>Section 4.1.2</u>, <font style="font-style: italic;">mutatis mutandis</font>. In addition, if Ionis provides GSK an Election Notice within ninety (90) days of such termination, then (A) GSK will (x) assign back to
                  Ionis any GSK Orange Book Patents (or any other Patent Rights) that relate to such Discontinued Products assigned by Ionis to GSK under this Agreement, and (y) transfer to Ionis for Ionis&#8217; use with respect to the Development and
                  Commercialization of the Discontinued Products, any Know-How data, results, regulatory information, filings, and files in the possession of GSK as of the date of the Election Notice that relate to such Discontinued Products, and any other
                  information or material specified in <u>Section 4.2.1</u> and (B) the licenses granted by Ionis under <u>Section 4.1.1</u> with respect to the Non-Assignable Ionis Product-Specific Patents shall terminate.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">2</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <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;">
      <div>
        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3a9716a938b549c1b901d64f297502be">

            <tr>
              <td style="width: 36pt; vertical-align: top; align: right; color: #000000; font-weight: bold;">3.</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><font style="font-weight: bold; color: #000000;"><u>Governing Law; Counterparts</u></font><font style="color: #000000;">.&#160; This Amendment No. </font>8<font style="color: #000000;"> and any dispute arising from the performance or
                    breach hereof will be governed by and construed and enforced in accordance with the laws of the State of Delaware, U.S.A., without reference to conflicts of laws principles.&#160; This Amendment No. 8 may be signed in counterparts, each and
                    every one of which will be deemed an original, notwithstanding variations in format or file designation which may result from the electronic transmission, storage and printing of copies of this Amendment No. 8 from separate computers or
                    printers.&#160; Facsimile signatures and signatures transmitted via PDF will be treated as original signatures.</font></div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(0, 0, 0);">*&#160; *&#160; *&#160; *</div>
    <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">[Signature page follows]</div>
    <div>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<br>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">3</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <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;">IN WITNESS WHEREOF</font>, the Parties have caused this Amendment No. 8 to be executed by their duly authorized representatives as of the Amendment No. 8 Effective Date.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z0264bf8697514956a50c5c8996358bdc">

        <tr>
          <td colspan="2" rowspan="1" style="width: 5%; vertical-align: top;">
            <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
          </td>
        </tr>
        <tr>
          <td rowspan="1" style="width: 5%; vertical-align: top;">&#160;</td>
          <td rowspan="1" style="width: 95%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>By:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>/s/ Brett Monia</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Name:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>Brett Monia</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Title:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>Chief Operating Officer</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Date:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>July 29, 2019</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="z4c86c2928f264c2299d3b276e39061d5">

        <tr>
          <td colspan="2" rowspan="1" style="width: 5%; vertical-align: top; font-weight: bold;">
            <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Glaxo Group Limited</div>
          </td>
        </tr>
        <tr>
          <td rowspan="1" style="width: 5%; vertical-align: top;">&#160;</td>
          <td rowspan="1" style="width: 95%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>By:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>/s/ Edinburgh Pharmaceutical Industries Limited, Corporate Director</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Name:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>Authorized Representative of Edinburgh Pharmaceuticals Industries Limited</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">&#160;</td>
          <td style="width: 95%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>By:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>/s/ The Wellcome Foundation Limited, Corporate Director</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Name:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>Authorized Representative of The Wellcome Foundation</u></div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="zb20e385c23e441ba9e4a5f5aab1bacb7">

        <tr>
          <td colspan="2" rowspan="1" style="width: 5%; vertical-align: top; font-weight: bold;">
            <div style="text-align: justify; font-variant: small-caps;">Glaxosmithkline intellectual property </div>
          </td>
        </tr>
        <tr>
          <td colspan="2" rowspan="1" style="width: 5%; vertical-align: top;">
            <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">development limited</div>
          </td>
        </tr>
        <tr>
          <td rowspan="1" style="width: 5%; vertical-align: top;">&#160;</td>
          <td rowspan="1" style="width: 95%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>By:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>/s/ Edinburgh Pharmaceutical Industries Limited, Corporate Director</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Name:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>Authorized Representative of Edinburgh Pharmaceuticals Industries Limited</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">&#160;</td>
          <td style="width: 95%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>By:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>/s/ Glaxo Group Limited, Corporate Director</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top;">
            <div>Name:</div>
          </td>
          <td style="width: 95%; vertical-align: top;">
            <div><u>Authorized Representative of Glaxo Group Limited</u></div>
          </td>
        </tr>

    </table>
    <div> <br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">4</font></div>
      <div style="page-break-after:always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      <div id="DSPFPageHeader"></div>
    </div>
    <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;"><u>APPENDIX A</u></div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;"><u>Non-Assignable Ionis Product-Specific Patents</u></div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(0, 0, 0);">[***]</div>
    <div style="text-align: center;">
      <div><br>
      </div>
      <div><br>
      </div>
      <font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">5</font></div>
  </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-10.3
<SEQUENCE>4
<FILENAME>ex10_3.htm
<DESCRIPTION>EXHIBIT 10.3
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 6.4.0.0
         Copyright 1995 - 2019 Broadridge -->
  </head>
<body bgcolor="#ffffff" style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;">






  <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>
    <div style="text-align: right; font-weight: bold;">EXHIBIT 10.3</div>
    <div style="font-weight: bold;"> <br>
    </div>
  </div>
  <div>
    <div>Midland Loan Services</div>
    <div>10851 Mastin Blvd., Suite 300</div>
    <div>Overland Park, Kansas&#160; 66210</div>
    <div style="text-align: justify;">Attention:&#160; Mr. Tad Janssen</div>
    <div>&#160;</div>
    <div style="text-align: right;">Loan Numbers:&#160; 030298801; 030298824; and 030298825</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">CONSENT TO COLLATERAL ADDITION AND AMENDMENT TO LOAN DOCUMENTS</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">This CONSENT TO COLLATERAL ADDITION AND AMENDMENT TO LOAN DOCUMENTS (this &#8220;<u>Agreement</u>&#8221;) is entered into as of August 1, 2019 by and among <font style="font-weight: bold;">IONIS GAZELLE, LLC</font>,
      a Delaware limited liability company (&#8220;<u>Borrower</u>&#8221;), with an address of 2855 Gazelle Court, Carlsbad, California 92010, <font style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</font>, a Delaware corporation (&#8220;<u>Principal</u>&#8221;), with an
      address of 2855 Gazelle Court, Carlsbad, California 92010, and <font style="font-weight: bold;">WELLS FARGO BANK, NATIONAL ASSOCIATION, AS TRUSTEE FOR THE BENEFIT OF THE REGISTERED HOLDERS OF UBS COMMERCIAL MORTGAGE TRUST 2017-C3, COMMERCIAL
        MORTGAGE PASS-THROUGH CERTIFICATES, SERIES 2017-C3</font> (&#8220;<u>Lender</u>&#8221;), with an address of c/o Midland Loan Services, a Division of PNC Bank, National Association, 10851 Mastin Boulevard, Suite 300, Overland Park, Kansas&#160; 66210, Re:&#160; Loan
      Numbers 030298801, 030298824, and 030298825.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;"><u>RECITALS</u></div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;"><font style="font-weight: normal;">A.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Borrower is the owner the property (the &#8220;<u>Original Property</u>&#8221;) encumbered by the Original Security Instrument (defined below) executed by Borrower, which
      Original Property is more particularly described in the Original Security Instrument.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">B.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;By assignment, Lender is the owner and holder of certain documents (collectively, the &#8220;<u>Original Loan Documents</u>&#8221;) evidencing, securing and otherwise pertaining to a loan (the &#8220;<u>Loan</u>&#8221;) made by UBS
      AG, by and through its branch office at 1285 Avenue of the Americas, New York, New York (&#8220;<u>Original Lender</u>&#8221;), to Borrower in the original principal amount of $51,350,000.00, including, without limitation, the following:</div>
    <div>&#160;</div>
    <div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z0a819112f1a441c8a4dc7f63f644c9d2">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(i)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Promissory Note A-1, dated July 18, 2017, in the original principal amount of $36,350,000.00, executed by Borrower, as maker, in favor of Original Lender (&#8220;<u>Note A-1</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zd8e032a3c9cd4587b9fbbfa583844039">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(ii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Promissory Note A-2, dated July 18, 2017, in the original principal amount of $5,000,000.00, executed by Borrower, as maker, in favor of Original Lender (&#8220;<u>Note A-2</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zbe5d27e951f947f791212dc70d5fc04a">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(iii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Promissory Note A-3, dated July 18, 2017, in the original principal amount of $10,000,000.00, executed by Borrower, as maker, in favor of Original Lender (&#8220;<u>Note A-3</u>&#8221;; and Note A-1, Note A-2 and Note A-3 are herein referred to
                    collectively as the &#8220;Note&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z6769da0287974585907da4ed748a536d">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(iv)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Loan Agreement, dated as of July 18, 2017, executed by Borrower and Original Lender (the &#8220;<u>Loan Agreement</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z75589ad469ba4afab88153a9c5195d56">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(v)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Deed of Trust and Security Agreement dated as of July 18, 2017, executed by Borrower in favor of Original Lender, filed for record in the Office of the Register of Deeds, Recorder of Deeds or County Clerk, as applicable, in and for
                    the County of San Diego, California (the &#8220;<u>Recording Office</u>&#8221;) as Document #2017-0323134, aforesaid records, as assigned to Lender pursuant to that certain Assignment of Deed of Trust and Security Agreement, recorded in the
                    Recording Office as Document #2017-0512265<font style="font-weight: bold;">&#160;</font>(the &#8220;<u>Original Security Instrument</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageFooter"></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0);"></div>
      </div>
      <!--PROfilePageNumberReset%Num%2%%%-->
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z3655713d5c074e45b7e95ba4184f5285">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(vi)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Assignment of Leases and Rents, dated as of July 18, 2017, executed by Borrower for the benefit of Original Lender, filed for record in the Recording Office as Document #2017-0323135, as assigned to Lender pursuant to that certain
                    Assignment of Assignment of Leases and Rents, recorded in the Recording Office as Document #2017-0512266<font style="font-weight: bold;">&#160;</font>(the &#8220;<u>Assignment of Leases</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z0d5ba37dd9464a20a9daa3e73c921ea4">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(vii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Environmental Indemnity Agreement, dated as of July 18, 2017, executed by Borrower and Principal in favor of Original Lender (the &#8220;<u>Environmental Indemnity</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z853766f84fa64ed4bc386409575af961">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(viii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Guaranty, dated as of July 18, 2017, executed by Principal in favor of Original Lender (the &#8220;<u>Guaranty</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z2d34d915b7584682af876320ea4a09a0">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(ix)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Cash Management Agreement, dated as of July 18, 2017, executed by Borrower, Original Lender and Wells Fargo Bank, N.A. (&#8220;<u>Wells</u>&#8221;);</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zd0d3cb2e372b4a2c80267c5633d9f8a3">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(x)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Deposit Account Control Agreement, dated as of July 18, 2017, executed by Borrower, Wells and Original Lender; and</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z35abdb83b37a4655bd3492100b4483d3">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(xi)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>certain UCC financing statements naming Borrower, as debtor, and Original Lender, as secured party, which financing statements have been assigned to Lender.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">The Original Loan Documents and all related documents, agreements, notes, certificates and financing statements evidencing or securing the Loan to which Borrower and/or Principal is a party (as
      amended or restated by this Agreement or the other New Loan Documents (defined below)), and this Agreement and the other New Loan Documents are hereinafter referred to collectively herein as the &#8220;<u>Loan Documents</u>&#8221;.&#160; Unless the context requires
      otherwise, references in this Agreement to the Loan Documents shall be deemed to refer to such documents as the same may be further amended, modified, supplemented, extended or replaced from time to time.&#160; Capitalized terms used but not defined
      herein have the meaning given such terms in the Loan Agreement, as amended hereby.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">C.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Midland Loan Services, a Division of PNC Bank, National Association (&#8220;<u>Servicer</u>&#8221;), services the Loan for Lender, as master servicer, pursuant to that certain Pooling and Servicing
      Agreement dated as of August 1, 2017 (the &#8220;<u>Pooling and Servicing Agreement</u>&#8221;).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">D.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;On the date hereof, (i) Principal conveyed to Borrower that certain parcel of land described on <u>Exhibit &#8220;A&#8221;</u> attached hereto (the &#8220;<u>Additional Parcel</u>&#8221;, and the Original
      Property and the Additional Parcel and all improvements and fixtures from time to time located on the Additional Parcel are herein sometimes referred to collectively as the &#8220;Property&#8221;) (such conveyance is referred to herein as the &#8220;<u>Conveyance</u>&#8221;);
      and (ii) Borrower and Principal entered into that certain Ground Lease dated as of the date hereof pursuant to which Borrower is leasing the entirety of the Additional Parcel to Principal (the &#8220;<u>Ground Lease</u>&#8221;).&#160; Principal intends to construct
      an approximately 70,000 square foot conference center (the &#8220;<u>Conference Center</u>&#8221;) and related improvements (collectively, the &#8220;<u>Improvements</u>&#8221;) in accordance with the plans and specifications for the Improvements delivered to Lender (as
      amended from time to time in accordance with the terms of this Agreement, the &#8220;<u>Plans</u>&#8221;), a description of which is attached hereto as <u>Exhibit B</u>, the budget for the Improvements delivered to Lender, a copy of which is attached hereto as
      <u>Exhibit C</u> (as amended from time to time in accordance with the terms of this Agreement, the &#8220;<u>Improvements Budget</u>&#8221;) and the construction timeline delivered to Lender (as amended from time to time in accordance with the terms of this
      Agreement, the &#8220;<u>Construction Timeline</u>&#8221;), a copy of which is attached hereto as <u>Exhibit D</u>.&#160; The Conveyance, the Ground Lease and the construction of the Improvements are collectively referred to herein as the &#8220;<u>Transactions</u>&#8221;.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">E.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Borrower and Principal have requested that Lender consent to the Transactions.&#160; Subject to the terms and conditions of this Agreement and the other New Loan Documents, Lender has agreed
      to consent to the Transactions.</div>
    <div>&#160;</div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">2</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: rgb(0, 0, 0); background-color: rgb(0, 0, 0);"></div>
    </div>
    <div style="text-align: center; font-weight: bold;"><u>AGREEMENT</u></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">NOW, THEREFORE, for good and valuable consideration, the receipt and adequacy of which is hereby acknowledged, the parties agree as follows:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">1.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; <font style="font-weight: bold;"><u>CONSENT TO TRANSACTIONS</u></font>. Subject to satisfaction of all of the terms and conditions contained in
      Section 3 hereof, Lender consents to the Transactions.&#160; This consent is strictly limited to the Transactions described in this Agreement.&#160; This Agreement shall not constitute a waiver or modification of any requirement of obtaining Lender&#8217;s consent
      (to the extent Lender&#8217;s consent is required by the Loan Documents) to any future acquisition of any property by Borrower or any future alteration or renovation of the Property, nor shall it constitute a modification of the terms, provisions, or
      requirements in the Original Loan Documents in any respect, except as expressly set forth herein, and the other New Loan Documents.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">2.</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;"><u>LOAN INFORMATION</u></font>. Borrower, Principal and Lender agree that as of the date
      hereof:</div>
    <div>&#160;</div>
    <div>
      <div style="text-align: justify;">
        <div>
          <div>
            <div>
              <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="za79c05a10d404a6995dfa7aab3b487a7" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

                  <tr style="vertical-align: top;">
                    <td style="width: 72pt;">&#160;</td>
                    <td style="vertical-align: top; width: 36pt;">
                      <div>(a)</div>
                    </td>
                    <td style="vertical-align: top; width: auto;">
                      <div>The outstanding principal balance of the Note is $51,350,000.00.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z3b8c8dc5c3234528bfe362110f129d88">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The interest rate of the Note is a fixed rate of 3.88% per annum.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zc54b06607086491886ddc5fc0823c7ce">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(c)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The maturity date of the Loan is August&#160;6, 2027.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z7fe8ab8a7d3847d6b548e4dd0b91e016">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(d)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The following listed payments are due and payable on the sixth (6th) day of each and every calendar month as of the Closing Date (as hereinafter defined):</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zee75914c120b4764b8aad58bbb54ea2c">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(i)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>interest installments only<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup>;</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z9ca8f447f4e74f03a59e6bba750a7d0c">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(ii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Monthly Tax Deposits<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup>;</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z6b8935424973423f8698b1ab5c15cf7f">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(iii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Monthly Insurance Deposits<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">3</sup>;</div>
                </td>
              </tr>

          </table>
          <div> <br>
          </div>
        </div>
      </div>
      <div>
        <div>
          <table cellspacing="0" cellpadding="0" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;" id="z7f89565c862a452383217f26f4a602ba" class="DSPFListTable">

              <tr style="vertical-align: top;">
                <td style="width: 108pt;">&#160;</td>
                <td style="vertical-align: top; width: 36pt;">
                  <div>(iv)</div>
                </td>
                <td style="align: left; vertical-align: top; width: auto;">
                  <div>$2,933.33&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Monthly Capital Expenditure Deposits<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">4</sup>; and</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div>
        <div>
          <table cellspacing="0" cellpadding="0" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;" id="z5d1c19ff39e740d5b196769e2719dc72" class="DSPFListTable">

              <tr style="vertical-align: top;">
                <td style="width: 108pt;">&#160;</td>
                <td style="vertical-align: top; width: 36pt;">
                  <div>(v)</div>
                </td>
                <td style="align: left; vertical-align: top; width: auto;">
                  <div>$29,333.33&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Monthly Rollover Deposit<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">5</sup>.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>
        <div><br>
        </div>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z9df61c3f83a94bdab2905795edf8a7cc">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top;">(e)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The current balance of each escrow account held by Lender with respect to the Loan is:</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" id="z1d2b5bafd83741018e8ccac5f3e86383" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 108pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>$00.00&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tax Account;</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" id="z3da33b2575904aee97da48e1ec46b1b5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 108pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(ii)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>$00.00&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Insurance Account;</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" id="zddf9da62bc29479eba0c244149caa210" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 108pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(iii)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>$00.00&#160; &#160; &#160; &#160; &#160; &#160; &#160; &#160; &#160; &#160; &#160; Capital Expenditures Account; and</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" id="zd8e383b19f7647c39335ace1899a8a9a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

                <tr>
                  <td style="width: 108pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(iv)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>$00.00&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Rollover Account.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
      </div>
      <div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z26d154b96dbd46668b904270c70aeabe">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(f)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>All required payments due through July 6, 2019 under the Loan Documents have been paid.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z0dbcbaca6baf4e34b084a21ec5170c4d">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top;">(g)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender is the current owner and holder of the Original Loan Documents.</div>
                  </td>
                </tr>

            </table>
            <div> <br>
            </div>
            <div>
              <hr noshade="noshade" align="left" style="background-color: rgb(0, 0, 0); border-width: medium; border-style: none; border-color: -moz-use-text-color; margin: 0px auto 0px 0px; height: 2px; width: 25%; color: rgb(0, 0, 0); text-align: left;"></div>
            <div> <br>
            </div>
          </div>
        </div>
      </div>
      <div>
        <div style="text-align: justify;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> The Loan is interest only until August 6, 2022.&#160; On September 6, 2022 and on each Monthly Payment Date thereafter until the maturity date, Borrower shall make monthly payments of principal and interest
          in the amount of $241,643.01.</div>
        <div>&#160;</div>
        <div style="text-align: justify;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup> The Monthly Tax Deposit is not required so long as each of the Tax Reserve Waiver Conditions Precedent are satisfied.</div>
        <div>&#160;</div>
        <div style="text-align: justify;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">3</sup> The Monthly Insurance Deposit is not required so long as each of the Insurance Reserve Waiver Conditions Precedent are satisfied.</div>
        <div>&#160;</div>
        <div style="text-align: justify;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">4</sup> The Monthly Capital Expenditure Deposit is not required so long as each of the Capital Expenditure Reserve Waiver Conditions Precedent are satisfied.</div>
        <div>&#160;</div>
        <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">5</sup> The Monthly Rollover Deposit is not required so long as each of the Rollover Reserve Waiver Conditions Precedent are satisfied.</div>
      </div>
      <div>&#160;</div>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">3</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">3.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <u></u><font style="font-weight: bold;"><u>CONDITIONS</u></font>. In addition to any other conditions set forth herein or
        required by Lender, the following are conditions precedent that must be satisfied prior to Lender&#8217;s consent to the Transactions set forth in this Agreement becoming effective (the &#8220;<u>Closing</u>&#8221; and the date all such conditions have been
        satisfied is herein referred to as the &#8220;<u>Closing Date</u>&#8221;):</div>
      <div>&#160;</div>
    </div>
  </div>
  <div><font style="font-weight: bold;"> </font></div>
  <div>
    <div>
      <div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcb73fcc87c7947538b3e51ce9d83010a">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>The execution and delivery of this Agreement by all of the parties hereto concurrently with the Closing.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z87a5da3c69de4d7f9e5a93fd91fa63f5">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of fully executed copies of the following documents (collectively, the &#8220;<u>Transaction Documents</u>&#8221;):&#160; (i) the Ground Lease in form and substance satisfactory to Lender, (ii) a subordination, non-disturbance and
                      attornment agreement for the Ground Lease in form and substance satisfactory to Lender, (iii) the &#8220;Construction Contracts&#8221; and other &#8220;Construction and Development Documents&#8221;&#160; (as such terms are defined hereinbelow) entered into by
                      Principal or obtained by Principal as of the date hereof.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze884a4b1986d49edadd60579d12259f2">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of evidence satisfactory to it that all insurance over the Property required by the Loan Documents (the &#8220;<u>Required Insurance</u>&#8221;) is in full force and effect as of the Closing, with all required premiums paid,
                      and contains a mortgagee&#8217;s clause (the &#8220;<u>Mortgagee&#8217;s Clause</u>&#8221;) satisfactory to Lender in favor of Lender, and its successors and/or assigns, c/o Midland Loan Services, Master Servicer, 10851 Mastin Boulevard, Suite 300, Overland
                      Park, Kansas 66210; re: Loan Numbers 030298801; 030298824; and 030298825.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zead96d6f877a4154a357c61b41c13159">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of a satisfactory Title Endorsement or Title Policy (as such terms hereinafter defined), or an irrevocable commitment by the applicable title company to issue such Title Endorsement or Title Policy.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3df37703f9ab40f882e57ed5f2b39334">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Borrower&#8217;s execution and delivery to Lender of the Settlement Statement (hereinafter defined) and Lender&#8217;s receipt of all of the Required Payments (hereinafter defined).</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3200e92b87544a759cde633b9b6180da">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(f)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Delivery to Lender of such legal opinions from counsel for Borrower and Principal as Lender may require, each in form and substance satisfactory to Lender.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6a372be603a84dd4a49a0e70b2770ccd">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(g)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of a REMIC opinion from counsel to Lender in form and substance satisfactory to Lender.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfe4b889fccdf4a8cb7f98a1b263e76ad">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(h)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of required third party consents (e.g., special servicer, directing certificateholder and rating agencies).</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd1bd3a5a91934030b81792879b554442">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of an IRS W9 form from Borrower and Principal.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z606da7ed599d4803b8bb14d8e19e60f4">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(j)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Lender&#8217;s receipt of evidence satisfactory to Lender of (i) the consummation of the Conveyance, which evidence shall include, without limitation, fully-executed copies of the quitclaim deed, closing statement and other documents
                      evidencing the Conveyance&#160; and (ii) the payment of all charges in connection with the Conveyance, including any transfer taxes.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div id="DSPFPageFooter"></div>
          <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">4</font></div>
          <div id="DSPFPageBreak" style="page-break-after: always;">
            <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;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfac339a358854db382d21c49f327deef">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(k)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Execution by Borrower and delivery to Lender of an Amended and Restated Deed of Trust and Security Agreement (the &#8220;<u>Restated Security Instrument</u>&#8221;) and an amendment to the Assignment of Leases (collectively, the &#8220;<u>Recorded
                        Documents Amendment</u>&#8221;) in form and substance satisfactory to Lender and the recordation thereof in the Recording Office.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z50d4f871500b491596ef1c6cccd81942">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(l)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>The recordation or filing, as applicable, of one or more amendments to existing financing statements amending the legal description attached thereto.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0e8d8a035c2b4bc1b4f2b33200f97b8e">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(m)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Receipt by Lender of a tenant estoppel certificate from Principal related to the Ground Lease in form and substance satisfactory to Lender.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7f20215d30c64bb99af19afe6719bf26">

                <tr>
                  <td style="width: 72pt;"><br>
                  </td>
                  <td style="width: 36pt; vertical-align: top; align: right;">(n)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>Approval by Lender of any amendments or modifications to Borrower&#8217;s operating agreement and Lender&#8217;s receipt of executed copies of same.</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
      </div>
      <div>
        <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">4.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>FEES, PAYMENTS AND EXPENSES</u></font>. Borrower covenants and agrees to pay to
          Lender, at Closing, the following (the &#8220;<u>Required Payments</u>&#8221;):</div>
        <div>&#160;</div>
      </div>
    </div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z774ca194c1a14dcca082d2484b3d82f9">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div>$192,562.50, which represents a consent fee for Lender&#8217;s consent to the Transactions.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0c104e69b22a4e0b970facdbb60540d5">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div>$3,850.00, which represents the attorneys&#8217; fees for the REMIC opinion.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z173a1568f9ed46e0a99576d6eb34929a">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div>$1,000.00, which represents the fees due Lender's environmental counsel.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9a488e28fe034c2393fe8dff108b2f48">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div>$2,362.00, which represents the fees due Omega Risk Management for its insurance review.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z879fdebbf6a74612ac36ff5e01c4b4f5">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div>$7,500.00, which represents fees due Fitch in connection with its review of the Transactions.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4ef7cd65b60b4fd182837ba4e155e5f0">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top; align: right;">(f)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div>$15,846.00, which represents fees due Kroll in connection with its review of the Transactions.</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">The Required Payments and any other fees, expenses and adjustments due and owing under the Loan Documents or in connection with the Transactions shall be paid in accordance with Lender&#8217;s settlement
      charges statement (the &#8220;<u>Settlement Statement</u>&#8221;) delivered at Closing for signature by Borrower.&#160; In addition, at Closing, Borrower shall pay all of Lender&#8217;s reasonable attorneys&#8217; fees and expenses incurred in connection with this Agreement and
      the Transactions in the amounts set forth on the Settlement Statement, which amounts shall be deemed Required Payments pursuant to the terms of this Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">5.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>TITLE ENDORSEMENT</u></font>.&#160; At Closing, Borrower shall (a)&#160;cause Fidelity National
      Title Insurance Company to issue such endorsements to Lender&#8217;s mortgagee title insurance policy (Policy No. 25008546L) in such form as Lender may require (collectively, the &#8220;<u>Title Endorsement</u>&#8221;), including, without limitation, showing that
      Borrower is the owner of the Property, showing Lender as the insured under such title policy, changing the effective date and time of such title policy (and all endorsements thereto) to the date and time of the recordation of the Restated Security
      Instrument, showing that the Restated Security Instrument is in a first lien position, and changing the legal description to match the legal description attached to the Restated Security Instrument and (b) pay the cost of the Title Endorsement, any
      escrow, filing or recording fees applicable to the Transactions, and any other costs and expenses incurred in connection with this Agreement or the Transactions.&#160; As an alternative to Borrower&#8217;s providing a Title Endorsement to Lender&#8217;s existing
      mortgagee title insurance policy, Borrower shall (a) provide at Closing to Lender a new mortgagee&#8217;s policy of title insurance issued by Fidelity National Title Insurance Company (the &#8220;<u>New Title Policy</u>&#8221;) providing the same title insurance
      coverage as provided in Lender&#8217;s existing mortgagee title insurance policy (including the endorsements thereto) with such changes as would be required by the Title Endorsement, including showing that Borrower is the owner of the Property, showing
      Lender as the insured under the New Title Policy, providing that the effective date and time of the New Title Policy is the date and time of the recordation of the Restated Security Instrument, and showing that the Restated Security Instrument is in
      a first lien position subject to no exceptions other than those set forth in Lender&#8217;s existing title policy and otherwise acceptable to Lender, which New Title Policy and endorsements thereto must be satisfactory to Lender in its sole and absolute
      discretion and (b) pay the cost of the New Title Policy, any escrow, filing or recording fees applicable to the Transactions, and any other costs and expenses incurred in connection with this Agreement or the Transactions.</div>
    <div>&#160;</div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">5</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <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; color: rgb(0, 0, 0);">6.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>RATIFICATION OF LOAN OBLIGATIONS</u></font>.&#160; Borrower hereby represents, warrants,
      acknowledges and agrees that, following the Transactions, all obligations and liabilities of Borrower under the Original Loan Documents, as modified by this Agreement and the other New Loan Documents, are and shall remain obligations and liabilities
      of Borrower.&#160; Borrower hereby expressly ratifies and confirms its obligation to pay the unpaid balance due and owing on the Loan and all interest thereon as provided in the Note and to pay and perform all other obligations under the Loan Documents to
      which it is a party.&#160; Borrower&#8217;s acknowledgment and ratification of the foregoing obligations (x) is absolute, unconditional and is not subject to any defenses, waivers, claims or offsets (including, without limitation, any defense that may arise as
      a result of or in connection with the Transactions) and (y) shall not be affected or impaired by any agreement, condition, statement or representation of any person or entity other than Lender.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Principal hereby represents, warrants, acknowledges and agrees that, following the Transactions, all obligations and liabilities of Principal under the Original Loan Documents, as modified herein or
      in the other New Loan Documents, to which it is a party shall be and remain obligations and liabilities of Principal.&#160; Principal hereby expressly ratifies and confirms all of its obligations under the Loan Documents to which it is a party.&#160;
      Principal&#8217;s acknowledgment and ratification of the foregoing obligations (x) is absolute, unconditional and is not subject to any defenses, waivers, claims or offsets (including, without limitation, any defense that may arise as a result of or in
      connection with the Transactions), and (y) shall not be affected or impaired by any agreement, condition, statement or representation of any person or entity other than Lender.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">7.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>NO REPRESENTATIONS OF LENDER</u></font>.&#160; Borrower and Principal agree that (a) neither
      Lender nor Servicer has made any representations or warranties, either express or implied regarding Borrower, Principal, the Loan or the Loan Documents, the Original Property, the Additional Parcel or the Improvements (including, without limitation,
      the Plans, the Improvements Budget, the Construction Timeline, or any of the Construction and Development Documents) or the effect of the Transactions on the Original Property or its value, use or operation, and Lender has and shall have no
      responsibility or liability whatsoever with respect to the Property or the construction of the Improvements or the effect thereof on the Property, including, without limitation, its value, its condition, or its use, occupancy or status, and (b) no
      claims relating to the Property or the construction of the Improvements or the effect thereof on the Property, including, without limitation, its value, its condition, or its use, occupancy or status, will be asserted against Lender or its agents,
      employees, professional consultants, affiliated entities, successors or assigns, either affirmatively or as a defense.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">8.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>BORROWER&#8217;S GENERAL REPRESENTATIONS, WARRANTIES AND COVENANTS</u></font>.&#160; Borrower
      hereby represents, warrants, and acknowledges to Lender, and agrees and covenants with Lender, that:</div>
    <div>&#160;</div>
    <div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd095ed30109e4af2bdaf6ca17791bc06">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower is the owner of the Property, and Borrower has the power to, and is duly authorized to, execute, deliver and perform (i) this Agreement and the other New Loan Documents to which it is a party and (ii) the Transaction
                    Documents to which it is a party and to consummate the Transactions and the other transactions contemplated hereby and thereby.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5bc5293083c84914b492b8d8231fdaf4">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Any court or third-party consents and/or approvals necessary for Borrower to enter into this (i) Agreement and the other New Loan Documents to which it is a party and (ii)&#160;the Transaction Documents to which it is a party and to
                    consummate the Transactions and the other transactions contemplated hereby and thereby have been obtained and remain in full force and effect.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageFooter"></div>
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">6</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <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;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z758baec8abd341e3b441b375bffa5ae9">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The entities and/or persons, as applicable, executing and delivering (i) this Agreement and the other New Loan Documents to which Borrower is a party and (ii)&#160;the Transaction Documents to which it is a party, on behalf of Borrower,
                    are duly authorized to so execute and deliver this Agreement and such other New Loan Documents and Transaction Documents.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z13fb10010b67411dab617789e43d755f">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>This Agreement, the other New Loan Documents to which it is a party and the other Loan Documents and Transaction Documents to which Borrower is a party are in full force and effect and the agreements and obligations of Borrower
                    contained herein and therein constitute and, following consummation of the Transactions shall continue to constitute, the valid and binding obligations of Borrower, enforceable against Borrower in accordance with their respective terms
                    and have not been modified either orally or in writing, except as expressly set forth herein.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze8b22185de904929b2875dec32d5844b">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There is no existing Default or Event of Default under any of the Loan Documents.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z507576bfe2b440be91030744e2c39a4a">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(f)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All taxes and assessments applicable to the Property that would be delinquent as of the Closing if not paid have been paid.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc3a70259c74843d3bb7830a2b8e95302">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(g)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There is no bankruptcy, receivership or insolvency proceeding pending or threatened in writing against Borrower.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4a5f0d201c95471aa54edfcdc2895ede">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(h)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower is not subject to any judgment, order, writ, injunction or consent decree.&#160; There are no actions, suits or proceedings pending or, to its knowledge, threatened in writing, (i)&#160;against or involving Borrower or the Property or
                    (ii)&#160;which relate to or may affect the Transactions or any of the other transactions contemplated by this Agreement, the other New Loan Documents or the other Loan Documents.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z67db9cdf4d8f436aacbcb3d53ab3a43b">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower has no intention to do any of the following prior to the Closing or within the 180 days following the Closing:&#160; (i) seek entry of any order for relief as debtor and a proceeding under the Code (hereinafter defined), (ii)
                    seek consent to or not contest the appointment of a receiver or trustee for itself or for all or any part of its property, (iii) file a petition seeking relief under any bankruptcy, arrangement, reorganization or other debtor relief
                    laws, or (iv) make a general assignment for the benefit of its creditors.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z744796b83e5c4469a06ce90f475b5bff">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(j)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All of the insurance required under the Loan Documents is in full force and effect, with all required premiums paid, and contains the required Mortgagee&#8217;s Clause.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5c121d870f4d480dafb5a2ab15024778">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(k)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower has no defenses, setoffs, claims, counterclaims or causes of action of any kind or nature whatsoever against Original Lender, Lender or any servicer of the Loan (including, without limitation, Servicer) with respect to or
                    arising out of (i) the Loan or the Loan Documents, including, without limitation, the administration or funding of the Loan, (ii) this Agreement or any of the other New Loan Documents or the transactions contemplated hereby or thereby,
                    or (iii) any acts or omissions of Original Lender,<font style="font-weight: bold;">&#160;</font>Lender<font style="font-weight: bold;">&#160;</font>or any servicer of the Loan (including, without limitation, Servicer) or any past or present
                    officers, agents or employees of Original Lender, Lender or any servicer of the Loan (including, without limitation, Servicer) and Borrower does hereby expressly waive, release and relinquish any and all such defenses, setoffs, claims,
                    counterclaims and causes of action, if any.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageFooter"></div>
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">7</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <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;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zda03d03d88094cf8a61b0b37b202de0a">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(l)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower has not requested that Lender waive, and to Borrower&#8217;s knowledge Lender has not waived, any requirements of the Loan Documents nor any of Lender&#8217;s rights thereunder.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z6adf7191a42c4eedbdd5bcec2faef013">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(m)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The Conveyance has been consummated, and the Ground Lease has been executed and delivered by Borrower and Principal.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc0568beb0926460d9a95838010324aff">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(n)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The ownership structure of Borrower is accurately described in each and every material respect on <u>Schedule&#160;3.1.28</u> attached to the Loan Agreement.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z24ea6bb281204a0fa5d86fdca367e399">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(o)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Neither the consummation of the Transactions nor Borrower&#8217;s execution and delivery of, and performance of its obligations under, this Agreement or the other New Loan Documents or the Transaction Documents to which it is a party will
                    violate, conflict with or result in a default under (i) any of its organizational documents, (ii) any law, rule, regulation, order, decree or judgment applicable to or binding upon Borrower or the Property, or (iii) any agreement or
                    other instrument to which Borrower is a party or by which Borrower or the Property is or may be bound or affected.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zba82139be68a42109cafd2680caf042a">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(p)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All information provided to Lender or Servicer by Borrower or any of its employees, officers, directors, partners, members, managers or representatives (and, to the best of Borrower&#8217;s knowledge, all information contained in any third
                    party report obtained by Borrower with respect to the Property), in connection with or relating to (i) this Agreement or the Transactions contemplated hereby or (ii) the Property contains no untrue statement of material fact and does
                    not omit a material fact necessary in order to make such information not misleading, and the provision of any such information by Lender or Servicer to any rating agency is expressly consented to by Borrower.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zea8372142d29438bbe2ddcc3da5def4d">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(q)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower is a limited liability company duly organized, validly existing and in good standing under the laws of the State of Delaware and is qualified to do business in the State of California, and there has not been any amendment,
                    modification or supplement to the certificate of formation, operating agreement or other organizational documents of Borrower since the date of the closing of the Loan.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdaf6a477366e46c0af0af6b201c82c9c">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(r)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>No funds used (or to be used) to close all or any part of the Transactions or to be used to construct the Improvements are secured, directly or indirectly, by an interest in Borrower, the Property or any other collateral for the
                    Loan.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7ccd3832cce94fc196aed033cb385421">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(s)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All representations and warranties of Borrower herein and in the Loan Documents to which it is a party and the certifications made by Borrower in that certain Officer&#8217;s Certificate delivered to Richards, Layton &amp; Finger, P.A.
                    with respect to the non-consolidation opinion are and shall be true and correct as of the date of this Agreement and the Closing and shall survive the Closing.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
    </div>
    <div style="text-align: justify;">Lender is entitled to rely, and has relied, upon these representations, warranties, acknowledgments, agreements and covenants in the execution and delivery of this Agreement and all other documents and instruments
      executed and delivered by Lender in connection with this Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify;">Borrower, by its execution of this Agreement, jointly and severally with Principal, agrees to reimburse, indemnify and hold Lender, its officers, agents, loan servicers (including, without limitation, Servicer) and
      employees harmless from and against any and all liabilities, judgments, costs, claims, damages, penalties, expenses, losses or charges (including, but not limited to, all legal fees and expenses and court costs), which may now or in the future be
      undertaken, suffered, paid, awarded, assessed or otherwise incurred as a result of or arising out of any breach or inaccuracy of the foregoing representations and warranties or any fraudulent conduct of Borrower in connection with this Agreement or
      the Transactions contemplated hereby, or the Property, including, without limitation, the misrepresentation of financial and other data presented to Lender in connection with the Transactions.</div>
    <div>&#160;</div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">8</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <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; color: rgb(0, 0, 0);">9.</font>&#160;&#160;&#160; &#160; &#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>PRINCIPAL&#8217;S GENERAL REPRESENTATIONS, WARRANTIES AND COVENANTS</u></font>.&#160; Principal
      hereby represents, warrants, and acknowledges to Lender, and agrees and covenants with Lender, that:</div>
    <div>&#160;</div>
    <div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z957170026d18471088bf9b0299848672">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Borrower is the owner of the Property.&#160; Principal has an unencumbered leasehold interest in the Improvements located on the Original Property pursuant to the Ionis Lease (as defined in the Original Loan Agreement) and an unencumbered
                    leasehold interest in the Additional Parcel pursuant to the Ground Lease.&#160; Upon the termination of the Ground Lease, all right, title and interest in and to all improvements located on the Additional Parcel (including, without
                    limitation, the Improvements) shall automatically vest in, and become the property of, the owner of the fee title to the Additional Parcel.&#160; Principal has the power to, and is duly authorized to, execute, deliver and perform (i) this
                    Agreement and the other New Loan Documents to which it is a party and (ii) the Transaction Documents to which it is a party and to consummate the Transactions and the other transactions contemplated hereby and thereby.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1afa01a2466a4fcba2be1b377e1383ab">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Any court or third-party consents and/or approvals necessary for Principal to enter into this Agreement, the other New Loan Documents to which it is a party and the Transaction Documents to which it is a party and to consummate the
                    Transactions and the other transactions contemplated hereby and thereby have been obtained and remain in full force and effect.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8a599631636849fe9101101c078a08f5">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The entities and/or persons, as applicable, executing and delivering (i) this Agreement and the other New Loan Documents to which Principal is a party and (ii)&#160;the Transaction Documents to which it is a party, on behalf of Principal,
                    are duly authorized to so execute and deliver this Agreement and such other New Loan Documents and Transaction Documents.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z996889195c274a9f8e36d7782c6c4ba9">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>This Agreement, the Guaranty, the Environmental Indemnity, the other New Loan Documents to which Principal is a party and the Transaction Documents to which Principal is a party are in full force and effect and the agreements and
                    obligations of Principal contained herein and therein constitute and, following the consummation of the Transactions, shall continue to constitute, the valid and binding obligations of Principal, enforceable against Principal in
                    accordance with their respective terms and have not been modified either orally or in writing, except for the modification to the Guaranty and Environmental Indemnity effectuated by this Agreement.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1c82bcf07524407a8ec43d43f67af707">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There is no existing Default or Event of Default under any of the Loan Documents.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za7aafc8bfb774ebfa424057a43f16bdb">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(f)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All taxes and assessments applicable to the Property that would be delinquent as of the Closing if not paid have been paid.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zcd334691e1ea4ea8a3af4d8ad1e4c012">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(g)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>There is no bankruptcy, receivership or insolvency proceeding pending or threatened in writing against Principal.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z719a8418cc78430f9400f0bc691f5a62">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(h)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Principal is not subject to any judgment, order, writ, injunction or consent decree. There are no actions, suits or proceedings pending or, to its knowledge, threatened in writing, (i)&#160;against or involving Principal that might
                    adversely affect Principal&#8217;s ability to perform under the Loan Documents to which it is a party, (ii) against, involving or relating to the Property or the construction of the Improvements, or (iii)&#160;which relate to or affect the
                    Transactions or any of the other transactions contemplated by this Agreement, the other New Loan Documents, the other Loan Documents or the Transaction Documents.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageFooter"></div>
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">9</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <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;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8684a03d68a24f60973160cd38062b80">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Principal has no intention to do any of the following prior to the Closing or within the 180 days following the Closing:&#160; (i) seek entry of any order for relief as debtor and a proceeding under the Code (hereinafter defined), (ii)
                    seek consent to or not contest the appointment of a receiver or trustee for itself or for all or any part of its property, (iii) file a petition seeking relief under any bankruptcy, arrangement, reorganization or other debtor relief
                    laws, or (iv) make a general assignment for the benefit of its creditors.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za0085e7aa0ab4157b86afcd97f20189d">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(j)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All of the insurance required under the Loan Documents is in full force and effect, with all required premiums paid, and contains the required Mortgagee&#8217;s Clause.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfe526c6682cc420189953869e42e24ce">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(k)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Principal has no defenses, setoffs, claims, counterclaims or causes of action of any kind or nature whatsoever against Original Lender, Lender or any servicer of the Loan (including, without limitation, Servicer) with respect to or
                    arising out of (i) the Loan or the Loan Documents, including, without limitation, the administration or funding of the Loan, (ii) this Agreement or any of the other New Loan Documents or the transactions contemplated hereby or thereby,
                    or (iii) any acts or omissions of Original Lender, Lender or any servicer of the Loan (including, without limitation, Servicer) or any past or present officers, agents or employees of Original Lender, Lender or any servicer of the Loan
                    (including, without limitation, Servicer) with respect to the Loan and Principal does hereby expressly waive, release and relinquish any and all such defenses, setoffs, claims, counterclaims and causes of action, if any.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc04eec11c1c24c95958fc00448783223">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(l)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Principal has not requested that Lender waive, and to Principal&#8217;s knowledge Lender has not waived, any requirements of the Loan Documents nor any of Lender&#8217;s rights thereunder.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zca765dc84bd546bcb347cfa90a1435f3">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(m)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The Conveyance has been consummated, and the Ground Lease has been executed by Borrower and Principal.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za066e8899fcc440785a874807d212925">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(n)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The ownership structure of Borrower is accurately described in each and every material respect on <u>Schedule&#160;3.1.28</u> attached to the Loan Agreement.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0e42e72899e54cf49722feff34e2fa13">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(o)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>Neither the consummation of the Transactions nor Principal&#8217;s execution and delivery of, and performance of its obligations under, this Agreement or the other New Loan Documents and the Transaction Documents to which it is a party
                    will violate, conflict with or result in a default under (i) any law, rule, regulation, order, decree or judgment applicable to or binding upon Principal or the Property, or (ii) any agreement or other instrument to which Principal is a
                    party or by which Principal or the Property is or may be bound or affected.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zde5bab04a607481585560a74f098019f">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(p)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All information provided to Lender or Servicer by Principal or any of its representatives (and, to the best of Principal&#8217;s knowledge, all information contained in any third party report obtained by Principal with respect to the
                    Property), in connection with or relating to (i) this Agreement or the Transactions contemplated hereby or (ii) the Property contains no untrue statement of material fact and does not omit a material fact necessary in order to make such
                    information not misleading, and the provision of any such information by Lender or Servicer to any rating agency is expressly consented to by Principal.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageFooter"></div>
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">10</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <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;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z212025e7e5c94fc681133399f5873836">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(q)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>No funds used (or to be used) to close all or any part of the Transactions or to be used to construct the Improvements are secured, directly or indirectly, by an interest in Borrower, the Property or any other collateral for the
                    Loan, or the Improvements.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z38b326e287bb438ca7f2646a41b3e323">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(r)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>The Existing Project has been completed in accordance with the terms of the Loan Agreement.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd006c9d739034e40a41a890ec357a656">

              <tr>
                <td style="width: 72pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(s)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div>All representations and warranties of Principal herein and in the Loan Documents to which it is a party and the certifications made by Principal in that certain Officer&#8217;s Certificate delivered to Richards, Layton &amp; Finger, P.A.
                    with respect to the non-consolidation opinion are and shall be true and correct as of the date of this Agreement and the Closing Date and shall survive the Closing.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
    </div>
    <div style="text-align: justify;">Lender is entitled to rely, and has relied, upon these representations, warranties, acknowledgments, agreements and covenants in the execution and delivery of this Agreement and all other documents and instruments
      executed and delivered by Lender in connection with this Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify;">Principal, by its execution of this Agreement, jointly and severally with Borrower, agrees to reimburse, indemnify and hold Lender, its officers, agents, loan servicers (including, without limitation, Servicer) and
      employees harmless from and against any and all liabilities, judgments, costs, claims, damages, penalties, expenses, losses or charges (including, but not limited to, all legal fees and court costs), which may now or in the future be undertaken,
      suffered, paid, awarded, assessed or otherwise incurred as a result of or arising out of any breach or inaccuracy of the foregoing representations and warranties or any fraudulent conduct of Principal in connection with this Agreement or the
      Transactions contemplated hereby, or the Property, including, without limitation, the misrepresentation of financial and other data presented to Lender in connection with the Transactions.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">10.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>REPRESENTATIONS AND COVENANTS REGARDING IMPROVEMENTS</u></font>.</div>
    <div>&#160;</div>
    <div>
      <div>
        <div>
          <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z90de71ccceb2446db6ff22fa205ff9a2" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

              <tr style="vertical-align: top;">
                <td style="width: 72pt;">&#160;</td>
                <td style="vertical-align: top; width: 36pt;">
                  <div style="text-align: justify;"><font style="text-align: left;"><font style="font-weight: normal;">(a)</font></font></div>
                </td>
                <td style="align: left; vertical-align: top; width: auto;">
                  <div style="text-align: justify;"><u>Definitions</u>.&#160; The parties hereto agree that, for purposes of this Agreement, the following terms shall have the meanings ascribed below unless the context clearly requires otherwise:</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
    </div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;"> <br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Architect</font>&#8221; means DG Architects, Inc. dba DGA.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Architect&#8217;s Agreement</font>&#8221; means that certain Owner/Architect Agreement dated November 28, 2018, entered into between Principal and the
      Architect, as the same has been amended and supplemented by Additional Service Requests 1-4.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Construction and Development Documents</font>&#8221; means the Construction Contracts, the Architect&#8217;s Agreement, the Plans, the Governmental
      Approvals, and all other instruments, documents and rights relating to the design, construction and development of the Improvements, together with all exhibits and attachments thereto.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Construction Contracts</font>&#8221; means the General Construction Contract and the Construction Management Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Construction Management Agreement</font>&#8221; means that certain letter agreement dated January 30, 2018, revised March 2, 2018 between Principal and
      Construction Manager relating to construction management services with respect to the Improvements.</div>
    <div>&#160;</div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageFooter"></div>
      <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">11</font></div>
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <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; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Construction Manager</font>&#8221; means Project Management Advisors, Inc., or such other construction manager as may be approved in writing by Lender
      prior to Principal&#8217;s engagement of such other construction manager.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Contractor</font>&#8221; means DPR Construction, a General Partnership.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;"><font style="font-weight: bold;">&#8220;Engineer&#8221; </font>means Pasco Larent Suitor &amp; Associates, Inc.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">General Construction Contract</font>&#8221; means that certain Standard Form of Agreement Between Owner and Construction Manager as Constructor where
      the basis of payment is the Cost of the Work Plus a Fee with a Guaranteed Maximum Price, dated August 28, 2018, between Principal and the Contractor.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 108pt;">&#8220;<font style="font-weight: bold;">Governmental Approvals</font>&#8221; means all consents, licenses, permits and all other authorizations or approvals required by any Governmental
      Authority, including, without limitation, that certain letter dated December 13, 2018 from Teri Delcamp, Principal Planner for the City of Carlsbad, California to Mr. Jon Olson of DGA Architects and all agreements entered into with any Governmental
      Authority, with respect to or in connection with the development, construction, completion, use and occupancy of the Improvements.</div>
    <div>&#160;</div>
    <div style="text-align: justify;">
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z4bd9e88297324c3cbd6e9cf62bba2638">

            <tr>
              <td style="width: 72pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;">(b)</td>
              <td style="width: auto; vertical-align: top; text-align: justify;">
                <div><u>Covenants</u>.&#160; Borrower and Principal covenant and agree with Lender as follows:</div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div>&#160;</div>
    <div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z931b2734425f4cc488eaeac1a5f98a82">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Construction</u>.&#160; Principal is and shall be solely responsible for the design, construction and completion of the Improvements and the payment of all costs and expenses in connection therewith and Borrower shall have no
                    obligations or liability under any Construction and Development Document or any other agreement relating to the design or construction of the Improvements.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2df417ea9d694ab29a11864aaabb0a5a">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(ii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Payment of Costs</u>.&#160; Principal agrees to, and Borrower agrees to cause Principal to, promptly pay all costs and expenses incurred in connection with the development of the Additional Parcel and the design and construction of the
                    Improvements as and when the same become due and payable.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8b22c0400c854d5e9e277d2bbb300af0">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;"><a name="z_Toc442184326"></a>(iii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Compliance With Construction and Development Documents and Other Agreements</u>.&#160; Principal agrees to, and Borrower agrees to cause Principal to, comply with the Construction and Development Documents to which Principal is a
                    party.&#160; Principal agrees to, and Borrower agrees to cause Principal to, deliver to Lender copies of any notices of default sent by or to Principal under or with respect to the Construction Contracts, the Architect&#8217;s Agreement, any
                    Governmental Approvals and any other agreement relating to the design, construction or development of the Improvements requiring payments of $500,000.00 or more, or under any REA in connection with or related to the design or
                    construction of the Improvements.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div id="DSPFPageFooter"></div>
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">12</font></div>
        <div id="DSPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
    </div>
    <div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc3d0c357ddb247bab248a16be17c6ade">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;"><a name="z_Ref363204852"></a><a name="z_Toc442184330"></a>(iv)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Construction and Completion of Improvements</u>.&#160; Principal has commenced construction of the Improvements but has ceased construction activity.&#160; Principal agrees to, and Borrower agrees to cause Principal to, recommence
                    construction of the Improvements on or before August 31, 2019 and thereafter Principal agrees to, and Borrower agrees to cause Principal to, diligently and continuously (subject to commercially reasonable reasons for delay (such as
                    force majeure events and unknown geological conditions)) prosecute the completion of construction of the Improvements in accordance with the Plans in a good and workmanlike matter, free of all defects (other than immaterial &#8220;punchlist&#8221;
                    items) and liens (other than those being contested in accordance with the terms hereof), and in compliance with the Construction and Development Documents, the Improvements Budget (as the same may be increased as permitted hereunder)
                    and all Legal Requirements including, without limitation, the REAs.&#160; The Improvements shall be completed in accordance with the terms of this Agreement prior to&#160; August 6, 2022.&#160; The Improvements shall comply with all Governmental
                    Approvals, all applicable Legal Requirements of all Governmental Authorities having jurisdiction over the Additional Parcel and all applicable insurance requirements (including, without limitation, applicable building codes, special use
                    permits, environmental regulations, and requirements of insurance underwriters) and any other restrictions encumbering the Additional Parcel, including, without limitation, the REAs.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfc7779d3a7564badb587f16c87fd95d8">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;"><a name="z_Ref363143048"></a><a name="z_Toc442184332"></a>(v)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Changes in Construction and Development Documents</u>.&#160; Lender&#8217;s approval shall not be required for changes in the Plans, the Improvements Budget, the Construction Timeline or the other Construction and Development Documents,
                    provided that Principal has obtained, and delivers to Lender with the quarterly reporting required hereunder copies of, all Governmental Approvals and other approvals required by or under any Legal Requirements (including the REA) in
                    connection with any changes in the Plans, the Improvements Budget, the Construction Timeline or other Construction and Development Documents and, with respect to amendments to the Construction Timeline, the completion date does not
                    extend beyond August 6, 2022.&#160; Principal shall (and Borrower agrees to cause Principal to) deliver to the Lender documentation as reasonably required by Lender pertaining to any change referred to in this Section.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z36ea7843308f4b73a5e358fc61163a90">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(vi)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Insurance</u>.&#160; In addition to any insurance required under the Loan Documents, at all times during the construction of the Improvements, Principal shall require that the general contractor name the Lender as additional insured
                    for ongoing and completed operations of the general contractors liability insurance.&#160; Principal shall deliver to Lender written evidence confirming its compliance herewith as requested by Lender from time to time.<a name="z_Ref363204892"></a><a name="z_Toc442184334"></a></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3f16e13db23d4eacbacb37e1c802b157">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(vii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Intentionally Omitted</u>.</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb5759dd7d1654aa7bda75107087a6ff1">

              <tr>
                <td style="width: 108pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;">(viii)</td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><u>Quarterly Deliverables</u>.&#160; <a name="z_Ref363747422"></a>Within ten (10) days after the end of each calendar quarter, Principal shall furnish to Lender and directly to Servicer at mlsassetmanagement@midlandls.com with a copy to
                    Chuck Hendricks, of Servicer, at chendric@midlandls.com, the following documents:</div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div>&#160;</div>
      <div>
        <div style="text-align: justify;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z50becd8a632b4d5ab798e90bee014a3f">

                <tr>
                  <td style="width: 144pt;"><br>
                  </td>
                  <td style="width: 31.5pt; vertical-align: top; align: right;">(a)</td>
                  <td style="width: auto; vertical-align: top; text-align: justify;">
                    <div>a report prepared by Construction Manager or the senior officer of Principal responsible for the oversight of the construction of the Improvements detailing the status of construction of the Improvements, including whether
                      construction is on, ahead of or behind the Construction Timeline and whether the construction of the Improvements is on budget and the cost to complete the Improvements in accordance with the Plans, all Legal Requirements and all
                      Governmental Approvals.&#160; Additionally, if any significant dispute arises between or among Principal, Contractor, Architect, or any subcontractor, supplier or any other party to a contract requiring payments, individually or in the
                      aggregate, equal to or greater than $500,000.00, said report will contain a written summary of the nature of such dispute;</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
        <div>&#160;</div>
        <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div id="DSPFPageFooter"></div>
          <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">13</font></div>
          <div id="DSPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
        </div>
        <div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z02a018fb444a40329ee85f5227db593b">

                  <tr>
                    <td style="width: 144pt;"><br>
                    </td>
                    <td style="width: 31.7pt; vertical-align: top; align: right;">(b)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>copies of all Governmental Approvals obtained for the construction of the Improvements in the prior calendar quarter;</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z14aa5006cc774475a31f8f669c1f4060">

                  <tr>
                    <td style="width: 144pt;"><br>
                    </td>
                    <td style="width: 31.7pt; vertical-align: top; align: right;">(c)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>copies of AIA Forms G702/703 for costs and invoices for all soft costs relating to the design or construction of the Improvements, in each case received by Principal in the prior calendar quarter and, upon Lender&#8217;s request,
                        Contractor and subcontractor invoices;</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zadfa79d9f04d449584268cd16624529d">

                  <tr>
                    <td style="width: 144pt;"><br>
                    </td>
                    <td style="width: 31.7pt; vertical-align: top; align: right;">(d)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>payment receipts and lien releases/waivers from the Contractor and all subcontractors under contracts having an aggregate payment obligation of $500,000.00 or more covering all payments in the prior calendar quarter;</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z3a54f010b8bc48328992214e68aa6e03">

                  <tr>
                    <td style="width: 144pt;"><br>
                    </td>
                    <td style="width: 31.7pt; vertical-align: top; align: right;">(e)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>copies of any (i) contracts relating to the design or construction of the Improvements for amounts equal to or greater than $500,000.00 entered into in the prior calendar quarter and (ii) changes to the Plans, Construction
                        Contracts, Architect&#8217;s Agreement or any construction or supply agreements having payments (individually or in the aggregate) equal to or greater than $500,000.00 (including change orders) made in the prior calendar quarter; and</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z60fd3d9906d7436aadcccccd550fded9">

                  <tr>
                    <td style="width: 144pt;"><br>
                    </td>
                    <td style="width: 31.7pt; vertical-align: top; align: right;">(f)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>copies of any amendments made to the Improvements Budget or Construction Timeline in the prior calendar quarter.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
        </div>
        <div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z339e09f7c509494983a63d95ddb94188">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(ix)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Liens</u>.&#160; Notwithstanding anything to the contrary contained in any Loan Document, any lien claimed or filed against any part of the Property for labor done or materials or services furnished in connection with the
                        construction of the Improvements shall be discharged, by bond or otherwise, within thirty (30) days after the date of Borrower&#8217;s or Principal&#8217;s receipt of actual notice of the filing thereof.&#160; Notwithstanding the foregoing, after
                        prior notice to Lender provided with said 30 day period, Principal, at its own expense, may contest by appropriate legal proceeding, conducted in good faith and with due diligence, the amount or validity of any claims (including
                        claims for labor, services, materials and supplies) for sums that have become due and payable and that by law have or may become a lien upon the Property (collectively, &#8220;Contestable Liens&#8221;); provided that (i) no Event of Default has
                        occurred and remains uncured; (ii) such proceeding shall be permitted under and be conducted in accordance with all applicable statutes, laws and ordinances, and the terms, conditions and provisions of any applicable document
                        encumbering the Property; (iii) neither the Property nor any part thereof or interest therein will be in danger of being sold, forfeited, terminated, canceled or lost; (iv) Principal shall promptly upon final determination thereof
                        pay the amount of any such Contestable Liens, together with all costs, interest and penalties which may be payable in connection therewith; (v) such proceeding shall suspend the collection of such Contestable Liens from the
                        Property; and (vi) Principal shall deposit with Lender cash, or other security as may be reasonably approved by Lender, in an amount equal to 110% of the contested amount (or such higher amount as may be required by applicable law),
                        to insure the payment of any such Contestable Liens, together with all interest and penalties thereon.&#160; Lender may pay over any such cash or other security held by Lender to the claimant entitled thereto at any time when, in the
                        reasonable judgment of Lender, the entitlement of such claimant is established.&#160; If Principal shall fail promptly to either (i)&#160;discharge any such lien, or (ii)&#160;post a bond which fully removes such lien within said thirty (30) day
                        period after the date of the filing thereof or (iii) contest such lien in accordance with the terms of this subsection, Lender may, at its election (but shall not be required to), procure the release and discharge of any such claim
                        and any judgment or decree thereon and, further, may in its sole discretion effect any settlement or compromise of the same, or may furnish such security or indemnity to the title insurer, and any amounts so expended by Lender,
                        including premiums paid or security furnished in connection with the issuance of bonds, shall be added to the Debt, shall be immediately due and payable, and shall bear interest at the Default Rate from the date of disbursement
                        until paid in full.&#160; In settling, compromising or discharging any claims for lien, Lender shall not be required to inquire into the validity or amount of any such claim.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">14</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
        </div>
        <div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zfecae44833ef4365ac29be93167c7833">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(x)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Notices</u>.&#160; Within ten&#160;(10) days after Borrower or Principal acquires knowledge of or receives notice of a defect in the Improvements or any departure from the Plans, or any other requirement of this Agreement, Borrower or
                        Principal, as applicable, will notify Lender and Principal shall proceed with diligence to correct all such defects and departures in accordance with the requirements contained herein.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0882e52602ce4ace9c2c2a1f2b6ec071">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(xi)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Cessation in Construction</u>.&#160; Once commenced, construction of the Improvements shall not be abandoned for a period of thirty (30) consecutive days or more, absent a commercially reasonable reason for doing so.&#160; Principal
                        shall promptly notify Lender if construction has stopped for a period of thirty (30) or more consecutive days and the reason therefor.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd8a7557e8c6b46baa001781b546c0c08">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(xii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>No Security Interest</u>.&#160; No materials, equipment, fixtures or articles of personal property placed in or on the Additional Parcel in connection with the construction of the Improvements shall be purchased by or installed
                        under any security agreement, financing lease or other agreement whereby the seller reserves or purports to reserve title, a lien, a security interest, the right of removal or repossession or the right to consider such items
                        personal property after their incorporation into the Improvements, unless previously authorized by Lender in writing.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd5af3dedb7f94d559bc469e1cf9bfc2f">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(xiii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Governmental and Other Approvals</u>.&#160; Principal is and shall be solely responsible for obtaining all necessary approvals in connection with all site work and construction of the Improvements, including, without limitation,
                        any approvals required under any REA and all Governmental Approvals, including, without limitation, certificates of completion and occupancy, required by any Governmental Authority or otherwise necessary for the construction, use,
                        occupancy and operation of the Improvements.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z32311e456c1b4c7eab3d64e65b568b64">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(xiv)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Construction and Development Documents</u>.&#160; Other than the New Loan Documents to which it is a party, Borrower has not entered into, and will not enter into, any contract or agreement (whether written or oral) in connection
                        with the development, construction or provision of labor, materials or design or supervisory services with respect to the Improvements.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">15</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z525db06c99e94ae39a90cbc66464dc9f">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(xv)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Obligation upon Completion</u>.&#160; Upon completion of the Improvements, (i) Principal shall deliver to Lender a certificate from the Architect that the Improvements have been completed in accordance with the Plans (in all
                        material respects), all applicable Governmental Approvals and all Legal Requirements, (ii) Principal shall provide to Lender written evidence reasonably acceptable to Lender in all respects that the Property continues to comply with
                        all applicable insurance requirements (including, without limitation, applicable building codes, special use permits, environmental regulations, and requirements of insurance underwriters) and any other restrictions encumbering the
                        Property, including, without limitation, the REAs; (iii) Borrower or Principal shall deliver to Lender a copy of the certificate of occupancy with respect to the Improvements and any other evidence obtained by Borrower or Principal
                        that the Improvements comply with all applicable Legal Requirements; (iv) Borrower shall cause to be issued and delivered to Lender an endorsement to the Title Insurance Policy insuring the continued priority of the Lien of the
                        Restated Security Instrument and evidence of payment of any premium payable in connection with such endorsement; (v) Principal shall deliver to Lender notice of such completion of the Improvements, together with an Officer&#8217;s
                        Certificate certifying that all of the requirements of this Section 10(b) have been satisfied; and (vi) within forty-five (45) days of the completion of the Improvements, Borrower or Principal shall deliver to Lender a Survey of the
                        Additional Parcel and the improvements thereon (including the Improvements) reasonably acceptable to Lender in all respects.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z286b45782cf440e89033667305ab725e">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(xvi)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Net Worth and Liquidity</u>.&#160; Principal agrees that until the Improvements have been completed in accordance with this Agreement, Principal shall maintain (x) a Net Worth of not less than $51,350,000.00 plus the estimated cost
                        of the Improvements (excluding Principal&#8217;s interest in the Original Property, Additional Parcel and Improvements) and (y) Liquid Assets of not less than $5,135,000.00 plus the estimated cost of the Improvements.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z979617316d78445d9c123291dc29742b">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Representation and Warranties</u><font style="font-weight: bold;">.&#160;&#160; </font>Borrower and Principal represent and warrant to Lender as follows:</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za5ee498caf1e4c1097f31d8d133a8240">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Governmental and Other Approvals</u>.&#160; All Governmental Approvals necessary to construct the Improvements in accordance with the Plans have been or will be obtained by Principal and are or will be valid and in full force and
                        effect, and in each case will remain as such.&#160; Principal has delivered true, correct and complete copies of all Governmental Approvals obtained by Principal to Lender as of the date hereof.&#160; The Improvements comply with all
                        applicable requirements set forth in the REAs, and all approvals required pursuant to the terms of any REA have been obtained by Borrower or Principal, as applicable, and copies of any such approvals have been provided to Lender.&#160;
                        To Borrower&#8217;s and Principal&#8217;s knowledge, the Improvements, if completed in accordance with the Plans, will comply with all applicable Governmental Approvals, all applicable Legal Requirements of all Governmental Authorities having
                        jurisdiction over the Additional Parcel and all applicable insurance requirements (including, without limitation, applicable building codes, special use permits, environmental regulations, and requirements of insurance underwriters)
                        and any other restrictions encumbering the Additional Parcel, including, without limitation, the REAs.<font style="font-weight: bold;">&#160; </font>Neither the construction nor use of the Improvements as a conference center with office
                        and uses ancillary thereto constitutes or will constitute or cause a violation, breach or default by Borrower or Principal under any Governmental Approval, Legal Requirement or document or agreement to which Borrower or Principal is
                        a party or the Original Property or Additional Parcel is bound. The Plans submitted to the City of Carlsbad, California (the &#8220;City&#8221;) and approved by the City are the same Plans heretofore delivered to Lender.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">16</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8f185fcd9afe4c26b1ad561598e16e25">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(ii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Plans</u>.&#160; As of the date hereof, the Plans (y) are satisfactory to Borrower and Principal and (z) have been approved by each Governmental Authority having jurisdiction over the Property and any others whose approval of the
                        Plans, in whole or in part, is required by any applicable Legal Requirement (including the REA).</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zdbd3080cbcc7485f9b6210b01d0e7fb6">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(iii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Construction and Development Documents</u>.&#160; Lender has been furnished true, correct and complete copies of all Construction and Development Documents entered into or obtained, as applicable, by Principal as of the date
                        hereof.&#160; As of the date hereof, the Architect&#8217;s Agreement and the Construction Contracts constitute all agreements executed by or for the benefit of Principal in connection with the design or construction of the Improvements.&#160; As of
                        the date hereof, the Architect&#8217;s Agreement and the Construction Contracts cover all work and services necessary or desirable for the design and construction of the Improvements, including all work and services necessary for the
                        Improvements to be completed in accordance with all Governmental Approvals and any and all requirements of all applicable Legal Requirements.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z98606a13b5054032bb66ed7efe8c31cf">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(iv)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Improvement Budget</u>.&#160; As of the date hereof, to the best of Principal&#8217;s knowledge after consultation with the Architect and Contractor, the Improvements Budget attached hereto as <u>Exhibit C</u> (x) is true, correct and
                        complete in all material respects, (y) shows all sources and uses of funds and (z) provides for all costs and expenses to be incurred in connection with the construction and equipping of the Improvements, and all other items of cost
                        and expense to be incurred in connection with the design and construction of the Improvements, including, without limitation, all costs and expenses to be incurred pursuant to the Construction and Development Documents.&#160; As of the
                        date hereof, neither&#160; Borrower nor Principal is aware of any other costs, expenses or fees which are material to the completion of the Improvements and are not covered by the Improvements Budget.&#160; The amount required to complete the
                        Improvements as set forth on the Improvements Budget ($54,718,029.00) is available and has been allocated by Principal in advance of the commencement of the construction of the Improvements and such amount shall be used solely to
                        complete the Improvements.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf1b1b198b98b47faafb67e13d91d7da0">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(v)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Utilities</u>.&#160; No utility or other municipal services necessary for the use and occupancy of the Original Property and improvements located thereon will be adversely affected by the construction of the Improvements.&#160; All
                        utility and municipal services necessary for the use and occupancy of the Improvements are currently available to the Adjacent Parcel.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0a0ac4822fa9470e8d68d27ae563fe27">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(vi)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Construction Timeline</u>.<font style="font-weight: bold;">&#160;</font>As of the date hereof, to the best of Principal&#8217;s knowledge after consultation with the Architect and Contractor, the Construction Timeline attached hereto as
                        <u>Exhibit D</u> (y) is true, correct and complete in all material respects, and (z) is a fair and reasonable timeline for completing the Improvements in accordance with the terms of this Agreement.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">17</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z45f7ee14cbc3411685c4c859eff1f763">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Right to Complete/Raze Improvements</u>.&#160; In addition to, and without limiting, any of Lender&#8217;s other rights and remedies under the Loan Documents, at law or in equity, Lender shall have the further right upon an Event of
                        Default under the Loan Agreement or any of the other Loan Documents, to enter the Property and take any and all actions necessary, in its judgment, to secure, protect and preserve the Improvements and any materials or supplies
                        located on the Property, to complete in part or in full the construction of the Improvements, including, but not limited to, making changes in the Plans (but not to the scope of the Improvements or the quality of the Improvements),
                        and entering into, and, subject to the terms thereof, modifying or terminating the Construction and Development Documents and other contractual arrangements.&#160; Alternatively, upon the occurrence of an Event of Default, Lender may
                        elect to demolish and remove any partially completed Improvements in accordance with all Legal Requirements.&#160; If Lender elects to continue with the construction of the Improvements or to demolish such Improvements, Lender will not
                        assume any liability to Borrower, Principal or any other Person for completing the Improvements or for the manner or quality of construction of the Improvements or for demolishing and removal of the Improvements and Borrower and
                        Principal each expressly waive any such liability, except to the extent that such liability shall be caused directly by the gross negligence or willful misconduct of Lender.&#160; Borrower and Principal each irrevocably appoint Lender&#160;
                        as its attorney-in-fact, with full power of substitution, to complete, upon exercise of the Lender's rights following an Event of Default, the Improvements in Borrower&#8217;s or Principal's name or the Lender may elect to complete
                        construction of the Improvements or demolish and remove the Improvements in the name of Lender or a subsidiary of Lender.&#160; In any event, all sums actually expended by Lender, or its subsidiary, in completing construction of the
                        Improvements, demolishing and removing the Improvements or otherwise exercising its rights hereunder or under the other Loan Documents will be part of the Debt, be secured by the Security Instrument and all other Loan Documents and
                        shall bear interest at the Default Rate.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze9e2754e5ee94d81b9a23df5e2894114">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Visitation and Inspection</u>.&#160; Borrower and Principal agree that the officers or authorized employees and agents (including any construction consultant engaged by Lender) of Lender or Servicer will have the right, upon not
                        less than forty-eight hours prior notice and at any reasonable time, to enter upon the Additional Parcel and inspect the construction work and all materials, plans, specifications and other matters relating to construction of the
                        Improvements. Borrower and Principal further agree that (i) neither Lender nor Servicer has any duty to examine, supervise or inspect the Plans, the Construction and Development Documents or the construction of the Improvements,
                        (ii) any inspection or examination by Lender, Servicer or their employees or agents is for the sole purpose of protecting the security interests granted in favor of the Lender and preserving its rights under this Agreement and the
                        other Loan Documents, (iii) no default or breach of Principal or Borrower will be waived by any inspection by Lender, Servicer or their employees or agents, nor will any such inspection constitute a representation that there has
                        been or will be compliance with the Plans or any other Construction and Development Documents or any Legal Requirement, or that the construction of the Improvements is free from defective materials or workmanship, (iv) no inspection
                        of the construction of the Improvements or any other inspection constitutes a warranty or representation by Lender or Servicer (or any of their employees or agents) as to the adequacy or safety of construction or any physical
                        condition or feature of the Additional Parcel or the Improvements and (v) neither Borrower nor Principal shall assert any position contrary to any of the foregoing</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">11.</font>&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>NO RELEASE OF BORROWER OR PRINCIPAL</u></font>.&#160; Each of Borrower and Principal
            hereby acknowledges, covenants and agrees that nothing contained in this Agreement or any other New Loan Document, the consummation of the Transactions or otherwise, shall be deemed or construed to release Borrower or Principal from any
            liability or other obligations under the Loan Documents to which it is a party, including, without limitation, Borrower&#8217;s liability under the terms of the Note and Security Instrument and Principal&#8217;s liability under the Guaranty. Each of
            Borrower&#8217;s and Principal&#8217;s acknowledgement of the foregoing obligations (i) is absolute, unconditional and is not subject to any defenses, waivers, claims or offsets, and (ii) shall not be affected or impaired by any agreement, condition,
            statement or representation of any person or entity.</div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">18</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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; color: rgb(0, 0, 0);">12.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>RELEASE OF LENDER</u></font>.&#160; Each of Borrower and Principal, for itself and for
            its agents, employees, representatives, officers, directors, general partners, limited partners, members, managers, shareholders, beneficiaries, trustees, administrators, subsidiaries, affiliates, servants, attorneys, heirs, successors and
            assigns (collectively, the &#8220;<u>Releasing Parties</u>&#8221;) jointly and severally release and forever discharge Original Lender, Lender and Servicer and each other servicer under the Pooling and Servicing Agreement, and their respective
            predecessors, successors, assigns, managers, partners, directors, officers, employees, agents, attorneys, administrators, trustees, subsidiaries, affiliates, beneficiaries, shareholders and representatives from all liabilities, obligations,
            costs, expenses, claims and damages, at law or in equity, known or unknown, which any of the Releasing Parties may now or hereafter hold or claim to hold under common law, statutory right or otherwise, arising in any manner out of, or relating
            to, any matters of any kind or nature whatsoever in connection with (x) the Property (including, without limitation, the ownership or operation thereof), the Loan (including, without limitation, the funding, administration or servicing
            thereof), any of the Loan Documents or any of the documents, instruments or any other transactions relating thereto or (y) the Ground Lease, the construction of the Improvements and the other transactions contemplated by the Loan Documents.&#160;
            Without limiting the generality of the foregoing, this release shall include the following matters: all aspects of this Agreement, the other New Loan Documents and the other Loan Documents and the transactions contemplated hereby and thereby,
            any negotiations, demands or requests with respect hereto or thereto.&#160; The Releasing Parties agree that this release is a full, final and complete release and that it may be pleaded as an absolute bar to any or all suit or suits pending or
            which may thereafter be filed or prosecuted by any of the Releasing Parties, or anyone claiming by, through or under any of the Releasing Parties.&#160; The Releasing Parties agree that this release is binding upon each of them and their respective
            agents, employees, representatives, officers, directors, general partners, limited partners, members, managers, shareholders, beneficiaries, trustees, administrators, subsidiaries, affiliates, servants, attorneys, heirs, successors and
            assigns.&#160; Lender agrees that the foregoing release does not apply to any act or omission of Lender first occurring after the Closing Date.</div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">13.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>REFERENCES IN THE LOAN DOCUMENTS</u></font>.&#160; The parties hereto hereby acknowledge
            and agree that the terms &#8220;Lender&#8221; and/or &#8220;Indemnitee&#8221; that may be contained in any of the Loan Documents shall be deemed to refer to Lender and its successors and/or assigns.&#160; From and after the date of this Agreement, this Agreement and the
            other New Loan Documents shall each be deemed a &#8220;Loan Document&#8221; for all purposes under the Loan Agreement and the other Loan Documents.</div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">14.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u></u><font style="font-weight: bold;"><u>RATIFICATION AND CONFIRMATION OF THE LOAN</u></font>.&#160; Borrower and
            Principal agree to perform each and every obligation under the Loan Documents to which it is a party, as specifically modified by this Agreement or the other New Loan Documents, and under any other loan documents to which it is a party executed
            on or about the date of this Agreement and evidencing, securing or otherwise relating to the Loan (this Agreement and such other loan documents being executed in connection herewith, collectively, the &#8220;<u>New Loan Documents</u>&#8221;) in accordance
            with their respective terms and conditions.&#160; Borrower and Principal ratify, affirm, reaffirm, acknowledge, confirm and agree that the Original Loan Documents to which it is a party or by which it is bound, as specifically modified by this
            Agreement or the other New Loan Documents, remain in full force and effect and, together with this Agreement and all other New Loan Documents to which it is a party or by which it is bound, represent legal, valid and binding obligations of each
            of Borrower and Principal, as applicable, enforceable against Borrower and Principal, as applicable, in accordance with their terms.&#160; Borrower and Principal hereby restate, ratify and confirm, as of the date hereof and after giving effect to
            each of the Transactions, each of the representations and warranties of Borrower or Principal, as applicable, under the Original Loan Documents, after giving effect to the modification affected by this Agreement and the other New Loan
            Documents, as if fully set forth herein.&#160; Without limiting the foregoing, Borrower acknowledges that the foregoing restatement of the representations and warranties in the Original Loan Documents (as so modified or restated) regarding the
            &#8220;Property&#8221; includes the Additional Parcel and the representations and warranties regarding the &#8220;Improvements&#8221; includes the Improvements (as defined herein).&#160; Borrower and Principal agree that neither this Agreement nor any other New Loan
            Document diminishes, impairs, releases or relinquishes the liens, powers, titles, security interests and rights securing or guaranteeing payment of the Loan, including the validity or first priority of the liens and security interests
            encumbering the Property granted Lender by the Loan Documents or the New Loan Documents.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">19</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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; color: rgb(0, 0, 0);">15.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>NONWAIVER</u></font>.&#160; The parties hereto acknowledge and agree that (a) any
            performance or non-performance of the Original Loan Documents prior to the date of this Agreement or Closing does not affect or diminish Lender&#8217;s ability to require future compliance with the Loan Documents, as the same may be modified from
            time to time in accordance with the terms thereof, and (b) in the future, Lender will require strict compliance with and performance of the Loan Documents, as the same may be modified from time to time in accordance with the terms thereof.&#160;
            Nothing contained herein shall be construed as a waiver of any of Lender&#8217;s rights or remedies with respect to any default, &#8220;Default&#8221; or &#8220;Event of Default&#8221; under this Agreement, any other New Loan Document and/or any other Loan Document.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">16.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>FURTHER ASSURANCES</u></font>.&#160; The parties hereto agree to do any act or execute
            any additional documents required by Lender, from time to time, to correct errors in the documenting of the Transactions, to effectuate the purposes of this Agreement or to better assure, convey, assign, transfer, perfect or confirm unto Lender
            the property and rights intended to be given it in the Loan Documents.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">17.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>LIABILITY</u></font>.&#160; If any party hereto consists of more than one person and/or
            entity, (a) the obligations and liabilities of each such person and/or entity hereunder shall be joint and several, (b) the representations, covenants and agreements of such party shall be deemed made by each person and/or entity comprising
            such party, and (c) each reference to such party shall be deemed a reference to each person and/or entity comprising such party. This Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective heirs,
            estates, legal representatives (acting on behalf of such party or its estate), successors and assigns forever.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">18.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>SEVERABILITY</u></font>.&#160; If any term, covenant or condition of this Agreement is
            held to be invalid, illegal or unenforceable in any respect, this Agreement shall be construed without such term, covenant or condition and the validity or enforceability of the remaining terms, covenants or conditions shall not in any way be
            affected.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">19.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>APPLICABLE LAW; JURISDICTION</u></font>.&#160; This Agreement shall be governed and
            construed in accordance with the laws of the State<font style="font-weight: bold;">&#160;</font>of New York.&#160; The parties hereto submit to personal jurisdiction in the state courts located in said state and the federal courts of the United States of
            America located in said state for the enforcement of any obligations hereunder and waive any and all personal rights under the law of any other state to object to jurisdiction within such state for the purposes of any action, suit, proceeding
            or litigation to enforce such obligations.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">20.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>DEFINITIONS</u></font>. Unless the context clearly indicates a contrary intent or
            unless otherwise specifically provided herein, words used in this Agreement (including pronouns) shall include the corresponding masculine, feminine or neuter forms, and the singular form of such words shall include the plural and vice versa.
            The words &#8220;included&#8221;, &#8220;includes&#8221; and &#8220;including&#8221; shall each be deemed to be followed by the phrase, &#8220;without limitation.&#8221;&#160; The words &#8220;herein&#8221;, &#8220;hereby&#8221;, &#8220;hereof&#8221;, and &#8220;hereunder&#8221; shall each be deemed to refer to this entire Agreement and not to
            any particular paragraph, article or section hereof.&#160; Notwithstanding the foregoing, if any law is amended so as to broaden the meaning of any term defined in it, such broader meaning shall apply subsequent to the effective date of such
            amendment.&#160; Where a defined term derives its meaning from a statutory reference, any regulatory definition is broader than the statutory reference and any reference or citation to a statute or regulation shall be deemed to include any
            amendments to that statute or regulation and judicial and administrative interpretations of it.</div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: #000000;">21.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>COMPLIANCE WITH ERISA</u></font>.&#160; As of the date of this Agreement, Borrower does not
            maintain any employee benefit plan which requires compliance with the Employee Retirement Income Security Act of 1974, as amended (&#8220;<u>ERISA</u>&#8221;).&#160; If at any time Borrower shall institute any employee benefit plans, it shall at all times
            comply with the requirements of ERISA.&#160; Principal shall at all times comply with the requirements of ERISA.</div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">20</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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; color: rgb(0, 0, 0);">22.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>SOLE DISCRETION OF LENDER</u></font>.&#160; Wherever pursuant to this Agreement, Lender
            exercises any right given to it to approve or disapprove, or any arrangement or term is to be satisfactory to Lender, Lender&#8217;s decision to approve or disapprove or to decide that arrangements or terms are satisfactory or not satisfactory shall
            be in the sole and absolute discretion of Lender and shall be final and conclusive, except as may be otherwise expressly and specifically provided herein.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">23.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>HEADINGS, ETC.</u></font> The headings and captions of various paragraphs of this
            Agreement are for convenience of reference only and are not to be construed as defining or limiting, in any way, the scope or intent of the provisions hereof.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">24.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>COUNTERPARTS</u></font>.&#160; This Agreement may be executed in any number of
            counterparts, each of which shall be deemed to be an original and all of which when taken together shall constitute one and the same agreement.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">25.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>INTEGRATION, SURVIVAL</u></font>.&#160; This Agreement, the other New Loan Documents and
            the Original Loan Documents, as modified or restated hereby or by another New Loan Document, embody the entire agreement by and between the parties hereto with respect to the Loan, and any and all prior correspondence, discussions or
            negotiations are deemed merged therein.&#160; Except as otherwise specifically provided herein, all obligations of any party contained in this Agreement, the other New Loan Documents or the Loan Documents, as modified hereby or by another New Loan
            Document, shall survive the Closing, and Lender hereby preserves all of its rights against all persons or entities and all collateral securing the Loan, including, without limitation, the Property.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">26.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>NO ORAL CHANGE</u></font>.&#160; This Agreement, and any provisions hereof, may not be
            modified, amended, waived, extended, changed, discharged or terminated orally or by any act or failure to act on the part of any party hereto, but only by an agreement in writing signed by the party against whom enforcement of any modification,
            amendment, waiver, extension, change, discharge or termination is sought. In addition, nothing contained in any document submitted for Lender&#8217;s review, including, without limitation any organizational documents of Borrower, Principal or any of
            their respective managers/members, partners, trustees or officers, shall modify, amend, waive, extend, change, discharge or terminate any term or provision of the Loan Documents or constitute Lender&#8217;s consent to any matter in the Loan Documents
            requiring Lender&#8217;s consent unless and until such time, if any, as an agreement specifically allowing such modification, amendment, waiver, extension, change, discharge or termination or consenting to such matter has been executed in writing by
            Lender.&#160; Furthermore, notwithstanding the delivery to Lender of any current title examinations and/or commitments for the Property, (a) this Agreement shall not constitute Lender&#8217;s consent or approval to the existence of any matters reflected
            in such title examinations and/or commitments to the extent such matters are not also reflected in the Lender&#8217;s mortgagee title insurance policy issued in connection with the Transactions and (b) Lender does not waive, shall not be deemed to
            have waived and hereby reserves, any and all rights it has under the Loan Documents, with respect to any lien or encumbrance on the Property not expressly permitted under the Loan Documents.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">27.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>NOTICES</u></font>.&#160; Except as otherwise specified herein, any notice, consent,
            request or other communication required or permitted hereunder shall be in writing and shall be deemed properly given if delivered in accordance with the notice requirements contained in the Loan Agreement using the address for a party hereto
            set forth at the top of the first page of this Agreement (as each such address may be changed from time to time by any such party by delivering notice thereof to the other parties hereto in the manner provided herein). Any notices or other
            communications required or permitted under any of the other Loan Documents shall be provided in accordance with the requirements therefor as set forth in each such Loan Document; <u>provided</u>, <u>however</u>, that from and after the date
            hereof the address of Lender, shall, subject to change as provided in the Loan Documents, be as set forth at the top of the first page of this Agreement.</div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">28.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>WAIVER OF JURY TRIAL</u></font>.&#160; <font style="font-weight: bold;">THE PARTIES
              HERETO KNOWINGLY, VOLUNTARILY AND INTENTIONALLY WAIVE ANY RIGHT THEY MAY HAVE TO A TRIAL BY JURY IN RESPECT OF ANY LITIGATION BASED ON THE LOAN OR ARISING OUT OF, UNDER OR IN CONNECTION WITH THIS AGREEMENT, THE OTHER NEW LOAN DOCUMENTS, OR
              THE OTHER LOAN DOCUMENTS, OR ANY COURSE OF CONDUCT, COURSE OF DEALING, STATEMENT (WHETHER VERBAL OR WRITTEN) OR ACTION OF ANY PARTY HERETO. THIS PROVISION IS A MATERIAL INDUCEMENT FOR LENDER&#8217;S CONSENT TO THE TRANSACTIONS.&#160; </font><font style="font-weight: bold;">EACH PARTY REPRESENTS AND WARRANTS THAT IT HAS REVIEWED THIS WAIVER WITH ITS LEGAL COUNSEL AND THAT IT KNOWINGLY AND VOLUNTARILY WAIVES ITS JURY TRIAL RIGHTS FOLLOWING CONSULTATION WITH LEGAL COUNSEL.</font></div>
          <div style="text-indent: 36pt;">&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">21</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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; color: rgb(0, 0, 0);">29.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>AMENDMENTS TO LOAN AGREEMENT</u>.&#160; </font>The following amendments to the Loan
            Agreement shall be effective as of the Closing Date:</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z1514856860ab4037ac2a5a8fa9c5f2a8">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Section 1.1 of the Loan Agreement is amended as follows:</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z023823db7b9c4842ab968850e307a32f">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>By inserting the following new defined term and definition thereof after the defined term &#8220;Condemnation&#8221;:</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt; margin-left: 144pt;">&#8220;&#8221;<u>Consent to Additional Collateral</u>&#8221; shall mean that certain Consent to Collateral Addition and Amendment to Loan Documents dated August 1, 2019 by and among Borrower,
            Guarantor and Lender.&#8221;</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7358dda2dbd948ec86dfca97f80f9ca5">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(ii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>By deleting the definition of &#8220;Ionis Lease&#8221; and inserting in lieu thereof the following new definition:</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt; margin-left: 144pt;">&#8220;&#8220;<u>Ionis Lease</u>&#8221; shall mean, collectively, (i) that certain Lease Agreement, dated as of the date hereof, between Ionis, as tenant and Borrower, as landlord, demising
            the Original Property (as defined in the Consent to Additional Collateral) to Ionis, as the same may be amended, restated, replaced, supplemented or otherwise modified from time to time in accordance with the terms of this Agreement and (ii)
            that certain Ground Lease, dated as of August 1, 2019, between Ionis, as tenant and Borrower, as landlord, demising the Additional Parcel (as defined in the Consent to Additional Collateral) to Ionis, as the same may be amended, restated,
            replaced, supplemented or otherwise modified from time to time in accordance with the terms of this Agreement.&#8221;</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc0aefe5f87784997920cff59769f4f1e">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(iii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>By inserting at the end of the definition of &#8220;Loan Documents&#8221; the following: &#8220;Loan Documents shall specifically include the Consent to Additional Collateral and any &#8220;New Loan Document&#8221; (as defined in the Consent to Additional
                        Collateral.&#8221;</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf5dd8989f8ad439b9bfc78d5afc37533">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(iv)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>By inserting at the end of the definition of the &#8220;Property&#8221; the following:&#160; &#8220;Notwithstanding anything to the contrary contained herein or in any other Loan Document, &#8220;Property&#8221; shall include the &#8220;Additional Parcel&#8221; (as defined in
                        the Consent to Additional Collateral) and all right, title and interest of Borrower in the improvements now or hereafter erected, situated or installed thereon and the personal property located therein.&#8221;</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z807f4a738a9d460380b25c3732179c82">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(v)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>By deleting the definition of &#8220;Security Instrument&#8221; and inserting in lieu thereof the following new definition:</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt; margin-left: 144pt;">&#8220;&#8220;<u>Security Instrument</u>&#8221; shall mean that certain first priority Amended and Restated Deed of Trust, Assignment of Leases and Rents, Security Agreement and Fixture
            Filing, dated as of August 1, 2019, executed and delivered by Borrower as security for the Loan and encumbering the Property, as the same may be amended, restated, replaced, supplemented or otherwise modified from time to time.&#8221;</div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">22</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze2135cffc459484a80f7289dacfa82ca">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Section 3.1.45 of the Loan Agreement is amended by inserting the following at the end thereof: &#8220;Additionally, upon completion of same, the Property will consist of an approximately 70,000 square foot conference center as
                        contemplated by the Consent to Additional Collateral.&#8221;</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd47965775d0847e7b7a40e1aa1f2ad11">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Section 10.1 of the Loan Agreement is amended (x) by deleting &#8220;or&#8221; at the end of clause (xviii), (y) by deleting the period at the end of clause (xix) and inserting &#8220;; or&#8221; in lieu thereof, and (z) inserting the following new
                        clauses (xx) and (xxi):</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt; margin-left: 144pt;">&#8220;(xx)&#160;&#160;&#160;&#160;&#160;&#160;&#160; If any of the representations and warranties made by Borrower or Guarantor in Section 10(c) of the Consent to Additional Collateral shall have been false or
            misleading in any material respect at the time such representation or warranty was made.</div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt; margin-left: 144pt;">(xxi)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If (I) Borrower or Guarantor shall default in the performance of any covenant contained in clauses (i), (iii) (with respect to delivery of notices only),
            (vi), (ix), (x), (xi), (xii), (xiv) or (xvi) of Section 10(b) of the Consent to Additional Collateral or (II) Guarantor shall default in the performance of the covenant contained in clause (viii) of Section 10(b) of the Consent to Additional
            Collateral and such default shall continue for more than ten (10) days after written notice to Guarantor from Lender; provided, however, notwithstanding the foregoing, Guarantor shall only be entitled to one notice of a default under Section
            10(b)(viii) per 365 day period and any subsequent default under section 10(b)(viii) within such 365 day period shall be an immediate Event of Default or (III) Borrower or Guarantor shall default in the performance of any covenant contained in
            Section 10(b) of the Consent to Additional Collateral other than those contained in clauses (i), (iii) (with respect to delivery of notices only), (vi), (viii), (ix), (x), (xi), (xii), (xiv) or (xvi) of Section 10(b), and if Borrower or
            Guarantor, as applicable, shall continue to be in default (y) for ten (10) days after written notice to Borrower or Guarantor, as applicable, from Lender, in the case of any default which can be cured by the payment of a sum of money, or (z)
            for thirty (30) days after written notice from Lender in the case of any other default; provided, however, that if such non-monetary default is susceptible of cure but cannot reasonably be cured within such thirty (30) day period and provided
            further that Borrower or Guarantor, as applicable, shall have commenced to cure such default within such thirty (30) day period and thereafter diligently and expeditiously proceeds to cure the same, such thirty (30) day period shall be extended
            for such time as is reasonably necessary for Borrower or Guarantor, as applicable, in the exercise of due diligence to cure such default, such additional period not to exceed sixty (60) days.&#8221;</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd14d79706bd64fa9a037b27219283ee5">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Section 11.22 of the Loan Agreement is amended by (i) inserting the following at the end of clause (xii) thereof:&#160; &#8220;including specifically, but without limitation, the &#8220;Improvements&#8221; (as defined in the Consent to Additional
                        Collateral), (ii) by deleting clause (xviii) in its entirety and inserting the following new clause (xviii) in lieu thereof: &#8220;(xviii) any indemnification and/or other obligations to the City of Carlsbad or any other Governmental
                        Authority or Person under any indemnification agreement, hold harmless agreement, maintenance agreement, notice of restrictions or other agreement of any kind or nature whatsoever executed by Guarantor and/or Borrower in connection
                        with or pursuant to any Governmental Approval or other consents and approvals issued in connection with the construction of the Improvements (as defined in the Consent to Additional Collateral) or the conveyance of the Additional
                        Parcel (as defined in the Consent to Additional Collateral)&#8221; (and (iii) by (x) deleting &#8220;or&#8221; at the end of clause (9) of the penultimate paragraph of Section 11.22, (y) deleting the period at the end of clause (10) of said paragraph
                        and inserting &#8220;; or&#8221; in lieu thereof and (z) inserting the following new clause (11): &#8220;(11) the &#8220;Improvements&#8221; (as defined in the Consent to Additional Collateral) have not been completed in accordance with the terms of the Consent
                        to Collateral Addition as of the date that is the earlier to occur of (A) August 6, 2025 or (B) the date Lender notifies Borrower in writing of the occurrence of an Event of Default under Sections 10.1(a)(i), (ii), (iii) or (iv) of
                        this Agreement&#8221;.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">23</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z30979e0b521f4fde9752d0d35ec31e77">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Schedule 3.1.22</u> attached to the Loan Agreement is hereby deleted in its entirely and is replaced with Schedule 3.1.22 attached hereto.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze001f55a46084fdbb05e3a499549e0a7">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(f)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div><u>Schedule 3.1.28</u> attached to the Loan Agreement is hereby deleted in its entirely and is replaced with Schedule 3.1.28 attached hereto.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">All references to the Loan Agreement in the Loan Documents shall be references to the Loan Agreement, as amended by this Agreement.</div>
          <div>&#160;</div>
          <div style="text-indent: 36pt;"><font style="font-weight: bold; color: rgb(0, 0, 0);">30.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;"><u>AMENDMENT TO ENVIRONMENTAL INDEMNITY</u></font>.&#160; The following amendments to the Environmental
            Indemnity shall be effective as of the Closing Date:</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5efe26411281452e8a692b2d8b7b37c0">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>All references in the Environmental Indemnity to &#8220;Environmental Report&#8221; shall be deemed to include references to that certain Phase I Environmental Site Assessment Report dated May 1, 2019, prepared by AEI Consultants in respect
                        of Lot 25.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z32f4103271624557bef0aeae111491db">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>All references in the Environmental Indemnity to &#8220;Property&#8221; shall mean the Original Property and the Additional Parcel and improvements located thereon.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div><br>
          </div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: #000000;">31.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>INTENTIONALLY OMITTED.</u></font></div>
          <div>&#160;</div>
          <div><br>
          </div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: #000000;">32.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>ANTI-MONEY LAUNDERING PROVISIONS</u></font>.</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z878bcf6b131c458fbe488e300cb393e7">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>For purposes of this Section 32:</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z87e02fa79c0444229a9e4a1ff50d9654">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(i)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Advances</u>&#8221; shall mean any and all disbursement of proceeds of the Loan funded by Lender to or for the benefit of Borrower in accordance with the terms and conditions set forth in the Loan Documents; <u>provided</u>, that
                        Lender has no further obligation to so disburse any such proceeds.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z8563dad2b6144120b3d9a96ced312978">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(ii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Anti-Terrorism Laws</u>&#8221; shall mean any Laws relating to terrorism, trade sanctions programs and embargoes, import/export licensing, money laundering or bribery, and any regulation, order, or directive promulgated, issued or
                        enforced pursuant to such Laws, all as amended, supplemented or replaced from time to time.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z9fc59c8b93a04be8b6d7e462b357bf29">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(iii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Collateral</u>&#8221; shall mean all real property and personal property now or hereafter securing the Loan, including, without limitation, the Property.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf128968f63194e6b848533676faa547f">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(iv)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Covered Entity</u>&#8221; shall mean (a) Borrower, each of Borrower&#8217;s subsidiaries, all guarantors under the Loan and all pledgors of Collateral and (b) each Person that, directly or indirectly, is in control of a Person described
                        in clause (a) above. For purposes of this definition, control of a Person shall mean the direct or indirect (x) ownership of, or power to vote, twenty-five percent (25%) or more of the issued and outstanding equity interests having
                        ordinary voting power for the election of directors of such Person or other Persons performing similar functions for such Person, or (y) power to direct or cause the direction of the management and policies of such Person whether by
                        ownership of equity interests, contract or otherwise.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">24</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zc3a59cf2544e452ab10e478a29f70fea">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(v)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Governmental Body</u>&#8221; shall mean any nation or government, any state or other political subdivision thereof or any entity, authority, agency, division or department exercising the executive, legislative, judicial, taxing,
                        regulatory or administrative powers or functions of or pertaining to a government (including any supra-national bodies such as the European Union or the European Central Bank) and any group or body charged with setting financial
                        accounting or regulatory capital rules or standards (including, without limitation, the Financial Accounting Standards Board, the Bank for International Settlements or the Basel Committee on Banking Supervision or any successor or
                        similar authority to any of the foregoing).</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z0f6d8a0f418b4bb8a8496750fa3dc6d0">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(vi)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Law(s)</u>&#8221; shall mean any law(s) (including common law), constitution, statute, treaty, regulation, rule, ordinance, opinion, issued guidance, release, ruling, order, executive order, injunction, writ, decree, bond,
                        judgment, authorization or approval, lien or award of or any settlement arrangement, by agreement, consent or otherwise, with any Governmental Body, foreign&#160; or domestic.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z2d0b047f2a2d40c4a34776283587c84c">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(vii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Person</u>&#8221; shall mean any individual, corporation, partnership (whether general or limited), joint venture, limited liability company, limited liability partnership, estate, trust, joint stock company, unincorporated
                        association, any federal, state, county or municipal government or political subdivision or any bureau, department or agency thereof and any fiduciary acting in such capacity on behalf of any of the foregoing or any other entity.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z187b7c5436e54794b606d624bdf1c512">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(viii)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Reportable Compliance Event</u>&#8221; shall mean that any Covered Entity becomes a Sanctioned Person, or is charged by indictment, criminal complaint or similar charging instrument, arraigned, or custodially detained in connection
                        with any Anti-Terrorism Law or any predicate crime to any Anti-Terrorism Law, or has knowledge of facts or circumstances to the effect that it is reasonably likely that any aspect of its operations is in actual or probable violation
                        of any Anti-Terrorism Law.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zd25c063a3be749d79fa304373369f679">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(ix)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Sanctioned Country</u>&#8221; shall mean a country subject to a sanctions program maintained under any Anti-Terrorism Law.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="za01b82f49dc34e328d2e1118c0873b1c">

                  <tr>
                    <td style="width: 108pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(x)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>&#8220;<u>Sanctioned Person</u>&#8221; shall mean any individual person, group, regime, entity or thing listed or otherwise recognized as a specially designated, prohibited, sanctioned or debarred person, group, regime, entity or thing, or
                        subject to any limitations or prohibitions (including but not limited to the blocking of property or rejection of transactions), under any Anti-Terrorism Law.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z7b6a73dac3984b0b9d69bb505aebd34f">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Borrower and Principal hereby warrant and represent to Lender that no Covered Entity is a Sanctioned Person, and that no Covered Entity, either in its own right or through any third party, (i) has any of its assets in a
                        Sanctioned Country or in the possession, custody or control of a Sanctioned Person in violation of any Anti-Terrorism Law; (ii) does business in or with, or derives any of its income from investments in or transactions with, any
                        Sanctioned Country or Sanctioned Person in violation of any Anti-Terrorism Law; or (iii) engages in any dealings or transactions prohibited by any Anti-Terrorism Law.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">25</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze1c07d01a44f48f8af31d5b7fb268743">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(c)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Borrower and Principal hereby covenant and agree with Lender that no Covered Entity will become a Sanctioned Person, and that no Covered Entity, either in its own right or through any third party, will (i) have any of its assets
                        in a Sanctioned Country or in the possession, custody or control of a Sanctioned Person in violation of any Anti-Terrorism Law; (ii) do business in or with, or derive any of its income from investments in or transactions with, any
                        Sanctioned Country or Sanctioned Person in violation of any Anti-Terrorism Law; (iii) engage in any dealings or transactions prohibited by any Anti-Terrorism Law; or (iv) use the Advances to fund any operations in, finance any
                        investments or activities in, or, make any payments to, a Sanctioned Country or Sanctioned Person in violation of any Anti-Terrorism Law. Borrower and Principal hereby further covenant and agree with Lender that the funds used to
                        repay the Debt will not be derived from any unlawful activity, and that each Covered Entity shall comply with all Anti-Terrorism Laws. Borrower covenants and agrees with Lender that Borrower shall promptly notify Lender in writing
                        upon the occurrence of a Reportable Compliance Event.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z29272864e63e4e9a88eaad740159d46a">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(d)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>It shall be an Event of Default under the Loan Documents if (i) any representation or warranty contained in Section 32(b) above is or becomes false or misleading at any time, or (ii) any covenant or agreement of Borrower or
                        Principal contained in Section 32(c) above is breached by Borrower or Principal, and, notwithstanding any provision to the contrary contained in any of the other Loan Documents, none of the Borrower or Principal shall be entitled to
                        (x) any notice of any such false or misleading warranty or representation or of any breach of any such covenant or agreement, nor to (y) any grace period or any cure right with respect to any such false or misleading warranty or
                        representation or any breach of any such covenant or agreement.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z5b9dba06e5d5495194d41ac2f7f0e5e1">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(e)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>If and to the extent that any of the other Loan Documents contain any anti-money laundering provisions, same are hereby deleted and shall be deemed to be replaced by the terms and provisions set forth in this Section 32.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold; color: #000000;">34.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><u>CFIUS</u></font>.</div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zb606a25e8b8f46f7a2e76a085dd3f7af">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(a)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Borrower hereby represents and warrants to Lender that neither Borrower&#8217;s acquisition of the Additional Parcel nor the Ground Lease is a Covered Transaction (as defined below).</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify;">
            <div>
              <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="zf1be404fcbaa4e0bbaec290b13a19ea2">

                  <tr>
                    <td style="width: 72pt;"><br>
                    </td>
                    <td style="width: 36pt; vertical-align: top; align: right;">(b)</td>
                    <td style="width: auto; vertical-align: top; text-align: justify;">
                      <div>Borrower and Principal agree that during the term of the Loan, Borrower and Principal shall, and shall cause the holders of direct and/or indirect, legal and/or beneficial, interests in Borrower (other than public shareholders of
                        Principal for so long as Principal is a publicly traded company on a recognized stock exchange in the United States of America) to, (a) within five (5) days of receipt of the same, notify Lender, and provide Lender with a copy of,
                        any inquiry received from CFIUS (as defined herein) or any other Governmental Authority related to<font style="font-weight: bold;">&#160;</font>each of the Borrower&#8217;s acquisition of the Additional Parcel and/or the Ground Lease, (b) make
                        any filing requested by CFIUS related to the Borrower&#8217;s acquisition of the Property and/or the Ground Lease, (c) cooperate with, and fully respond to any CFIUS Review related to the Borrower&#8217;s acquisition of the Property and/or the
                        Ground Lease, in each case within the time permitted by CFIUS or such Governmental Authority, as applicable, and (d) subject to the terms and conditions of the Loan Documents, take any mitigation measures requested by CFIUS and/or
                        any Governmental Authority in connection with the CFIUS Review.</div>
                    </td>
                  </tr>

              </table>
            </div>
          </div>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">For purposes of this Section:</div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">26</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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; margin-left: 36pt;">&#8220;<font style="font-weight: bold;"><u>CFIUS</u></font>&#8221; shall mean (i)&#160;the Committee on Foreign Investment in the United States first established pursuant to Executive Order 11858 of May 7,
            1975, and (ii)&#160;any replacement or successor thereto, including, without limitation, pursuant to FIRRMA.</div>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;"><u>CFIUS Review</u></font>&#8221; shall mean CFIUS&#8217;s review and/or investigation, including any inquiries received from, CFIUS or any Governmental Authority related
            to CFIUS&#8217;s review and/or investigation.</div>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;"><u>Covered Transaction</u></font>&#8221; shall have the meaning set forth in the DPA.</div>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;"><u>DPA</u></font>&#8221; shall mean the Defense Production Act of 1950, 50&#160;U.S.C. &#167;&#160;4565, as amended by FIRRMA, H. R. 5515-538 (as the same may have been or may
            hereafter be amended, restated, supplemented or otherwise modified), all laws and regulations related thereto and all mandates, requirements, powers and similar requirements imposed or exercised thereunder (including, without limitation, any of
            the foregoing implemented by and/or otherwise relating to CFIUS), as the foregoing may be amended from time to time, any successor statute or statutes and all rules and regulations from time to time promulgated in connection with the foregoing.</div>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;"><u>FIRRMA</u></font>&#8221; shall mean the Foreign Investment Risk Review Modernization Act of 2018.</div>
          <div>&#160;</div>
          <div style="text-align: justify; margin-left: 36pt;">&#8220;<font style="font-weight: bold;"><u>Governmental Authority</u></font>&#8221; shall mean any court, board, agency, commission, office or authority of any nature whatsoever or any governmental unit
            (federal, state, county, district, municipal, city, foreign or otherwise) whether now or hereafter in existence.</div>
          <div>&#160;</div>
          <div style="text-align: center; font-style: italic;">[remainder of page intentionally left blank]</div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">27</font></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <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;">IN WITNESS WHEREOF,</font> the parties hereto have caused this Agreement to be executed under seal by their duly authorized representatives as of the day, month
            and year first above written.</div>
          <div>&#160;</div>
          <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z1c1b883623e7463fa3e7a1a632c415e3">

              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="2" style="vertical-align: top;">
                  <div style="font-weight: bold;">BORROWER:</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="2" style="vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="2" style="vertical-align: top;">
                  <div><font style="font-weight: bold;">IONIS GAZELLE, LLC</font>, a Delaware limited liability company</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="2" style="vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">
                  <div>By:</div>
                </td>
                <td style="width: 47%; vertical-align: top;">
                  <div>Ionis Pharmaceuticals, Inc., a Delaware corporation, its sole member</div>
                </td>
              </tr>

          </table>
          <div><br>
          </div>
          <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zc05f085b2cf147c39b960045440e7df7">

              <tr>
                <td style="width: 53%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>By:</div>
                </td>
                <td style="width: 42%; vertical-align: top;">
                  <div><u>/s/ Elizabeth L. Hougen</u></div>
                </td>
              </tr>
              <tr>
                <td style="width: 53%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>Name:</div>
                </td>
                <td style="width: 42%; vertical-align: top;">
                  <div>Elizabeth L. Hougen</div>
                </td>
              </tr>
              <tr>
                <td style="width: 53%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>Title:</div>
                </td>
                <td style="width: 42%; vertical-align: top;">
                  <div>Senior Vice President, Finance and Chief</div>
                </td>
              </tr>
              <tr>
                <td style="width: 53%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">&#160;</td>
                <td style="width: 42%; vertical-align: top;">
                  <div>Financial Officer</div>
                </td>
              </tr>

          </table>
          <div><br>
          </div>
          <div style="text-align: center; font-style: italic;">[signatures continue on next page]</div>
          <div>&#160;
            <div style="text-align: center; font-size: 8pt; font-weight: bold;">[SIGNATURE PAGE TO CONSENT TO COLLATERAL ADDITION AND AMENDMENT TO LOAN DOCUMENTS]</div>
            <div style="text-align: center; font-size: 8pt; font-weight: bold;"> <br>
            </div>
          </div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z152f7c510ff94e6aa2da2b659c953bba">

              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="2" style="vertical-align: top;">
                  <div style="font-weight: bold;">PRINCIPAL:</div>
                </td>
              </tr>
              <tr>
                <td rowspan="1" style="width: 50%; vertical-align: top;">&#160;</td>
                <td rowspan="1" colspan="2" style="vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="2" style="vertical-align: top;">
                  <div><font style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</font>, a Delaware corporation</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">&#160;</td>
                <td style="width: 45%; vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>By:</div>
                </td>
                <td style="width: 45%; vertical-align: top;">
                  <div><u>/s/ Elizabeth L. Hougen</u></div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>Name:</div>
                </td>
                <td style="width: 45%; vertical-align: top;">
                  <div>Elizabeth L. Hougen</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>Title:</div>
                </td>
                <td style="width: 45%; vertical-align: top;">
                  <div>Senior Vice President, Finance and Chief</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">&#160;</td>
                <td style="width: 45%; vertical-align: top;">
                  <div>Financial Officer</div>
                </td>
              </tr>

          </table>
          <div><br>
          </div>
          <div style="text-align: center; font-style: italic;">[signatures continue on next page]</div>
          <div>&#160;
            <div style="text-align: center; font-size: 8pt; font-weight: bold;">[SIGNATURE PAGE TO CONSENT TO COLLATERAL ADDITION AND AMENDMENT TO LOAN DOCUMENTS]</div>
          </div>
          <div><br>
          </div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="za08ac3b1d4074e7f8b7ad55017418957">

              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="3" style="vertical-align: top;">
                  <div style="font-weight: bold;">LENDER:</div>
                </td>
              </tr>
              <tr>
                <td rowspan="1" style="width: 50%; vertical-align: top;">&#160;</td>
                <td rowspan="1" colspan="3" style="vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td colspan="3" style="vertical-align: top;">
                  <div style="font-weight: bold;">WELLS FARGO BANK, NATIONAL ASSOCIATION, AS TRUSTEE FOR THE BENEFIT OF THE REGISTERED HOLDERS OF UBS COMMERCIAL MORTGAGE TRUST 2017-C3, COMMERCIAL MORTGAGE PASS-THROUGH CERTIFICATES, SERIES 2017-C3</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">&#160;</td>
                <td style="width: 42%; vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">
                  <div>By:</div>
                </td>
                <td colspan="2" style="vertical-align: top;">
                  <div>Midland Loan Services, a Division of PNC Bank, National Association, its Attorney-in-Fact</div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">&#160;</td>
                <td style="width: 42%; vertical-align: top;">&#160;</td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>By:</div>
                </td>
                <td style="width: 42%; vertical-align: top;">
                  <div><u>/s/ Alan H. Torgler</u></div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>Name:</div>
                </td>
                <td style="width: 42%; vertical-align: top;">
                  <div><u>Alan H. Torgler</u></div>
                </td>
              </tr>
              <tr>
                <td style="width: 50%; vertical-align: top;">&#160;</td>
                <td style="width: 3%; vertical-align: top;">&#160;</td>
                <td style="width: 5%; vertical-align: top;">
                  <div>Title:</div>
                </td>
                <td style="width: 42%; vertical-align: top;">
                  <div><u>Vice President, Servicing Officer</u></div>
                </td>
              </tr>

          </table>
          <div><br>
          </div>
          <div>
            <div style="text-align: center; font-size: 8pt; font-weight: bold;">[SIGNATURE PAGE TO CONSENT TO COLLATERAL ADDITION AND AMENDMENT TO LOAN DOCUMENTS]</div>
            <div style="font-size: 8pt; font-weight: bold;"> <br>
            </div>
          </div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <div style="text-align: center; font-weight: bold;"><u>EXHIBIT &#8220;A&#8221;</u></div>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;"><u>Additional Parcel</u></div>
          <div>&#160;</div>
          <div>LOT 25 OF CARLSBAD TRACT NO. 97-13-03, CARLSBAD OAKS NORTH PHASE 3, ACCORDING TO MAP THEREOF NO. 16145, RECORDED IN THE OFFICE OF THE COUNTY RECORDER OF SAN DIEGO COUNTY, CALIFORNIA, ON OCTOBER 13, 2016 AS DOCUMENT NO. 2016-7000438 OF
            OFFICIAL RECORDS.</div>
          <div><br>
          </div>
          <div>APN: 209-120-27-00</div>
          <div><br>
          </div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
          </div>
          <div style="text-align: center; font-weight: bold;"><u>EXHIBIT &#8220;B&#8221;</u></div>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;"><u>Plans</u></div>
          <div>&#160;</div>
          <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
            <div id="DSPFPageFooter"></div>
            <div style="page-break-after:always;" id="DSPFPageBreak">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            <div id="DSPFPageHeader"></div>
          </div>
          <div style="text-align: center; font-weight: bold;"><u>EXHIBIT &#8220;C&#8221;</u></div>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;"><u>Improvements Budget</u></div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            <div id="DSPFPageHeader"></div>
          </div>
          <div style="text-align: center; font-weight: bold;"><u>EXHIBIT &#8220;D&#8221;</u></div>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;"><u>Construction Timeline</u></div>
          <div>&#160;</div>
          <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
            <div id="DSPFPageFooter"></div>
            <div id="DSPFPageBreak" style="page-break-after: always;">
              <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
            <div id="DSPFPageHeader"></div>
          </div>
          <div style="text-align: center; font-weight: bold;"><u>SCHEDULE 3.1.22</u></div>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;"><u>RENT ROLL</u></div>
          <div>&#160;</div>
          <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
            <div id="DSPFPageFooter"></div>
            <div style="page-break-after:always;" id="DSPFPageBreak">
              <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
            <div id="DSPFPageHeader"></div>
          </div>
          <div style="text-align: center; font-weight: bold;"><u>SCHEDULE 3.1.28</u></div>
          <div>&#160;</div>
          <div style="text-align: center; font-weight: bold;"><u>ORGANIZATIONAL CHART</u></div>
          <div>&#160;</div>
          <br>
          <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>
      </div>
    </div>
  </div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>5
<FILENAME>ex31_1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 6.4.0.0
         Copyright 1995 - 2019 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'; font-size: 10pt;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center">EXHIBIT 31.1</div><div><br></div><div style="text-align: center; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I, Stanley T. Crooke, certify that:</div><div><br></div><div style="text-align: justify;"><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="zf0321ac4bb7f47fcbc8806ce94d49f4c"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</div></td></tr></table></div></div><div><br></div><div style="text-align: justify;"><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="za0cb7910e2964026bca7affed4fb0a6f"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z71c4b62910b8423fa842c6875af6043c"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z6815892e04104e82908af487e1999649"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z943deb47116e425898b380e6581421d6"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z596e59070f56478c8a31fb5d43ecda45"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="zea2adfeacf244549a68a1d09355e5ca7"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z5522a56303c04b79806fb1a7c67f6e44"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z0456be0653834aa8ad13b13b06d20cbb"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">5.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z42cbfcd5267f48628163b99f7c4cc4fb"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z0c9c501328a44fdd83d371e2cdeb9c18"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; 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="z064c4fca4db6485bb6361df973b42842"><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Dated: November 6, 2019</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">/s/ STANLEY T. CROOKE</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Stanley T. Crooke, M.D., Ph.D.</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><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>6
<FILENAME>ex31_2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 6.4.0.0
         Copyright 1995 - 2019 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'; font-size: 10pt;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center">EXHIBIT 31.2</div><div><br></div><div style="text-align: center; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I, Elizabeth L. Hougen, certify that:</div><div><br></div><div style="text-align: justify;"><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="zfe1333d482244e079d4607bfcad5b28a"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q of Ionis Pharmaceuticals, Inc.;</div></td></tr></table></div></div><div><br></div><div style="text-align: justify;"><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="ze66bdf84d1bc4a1fba48db2c636bbc66"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z89fcda79029f40a4a79ceca8ad6252e7"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z43eeaa0e2a7c4c0eb09a0f480416d20c"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="zcbca58727c454c578a2c48fdd735eeed"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="zb39eb837fe5b406ea6bd9b909e1be03e"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z85217b8b9fb94ad8853591915a35360c"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z72f55c6f9c494926bcf125fdde039875"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z79f7cdde97a24b9a8cf674ec700a8dd2"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">5.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="zd75dc4a82d8c44238226ebac624f230f"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><div><br></div><div style="text-align: justify;"><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="z584f4c20e97e46fa92f00f4c1ce1ea80"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">b)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><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="z5dd2f3a72dd34a519dc847f670347887"><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><a name="z3a893fc63bc44c8c8146b8729339adbf"><!--Anchor--></a>Dated: November 6, 2019</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Elizabeth L. Hougen</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Chief Financial Officer</div></td><td style="width: 72.25%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><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>7
<FILENAME>ex32_1.htm
<DESCRIPTION>EXHIBIT 32.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 6.4.0.0
         Copyright 1995 - 2019 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'; font-size: 10pt;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center">Exhibit 32.1</div><div><br></div><div style="text-align: center; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; text-indent: 36pt; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, Stanley T. Crooke, 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><div style="text-align: justify;"><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="z19a059afd5254addb56415aba518859f"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">The Company&#8217;s Quarterly Report on Form 10-Q for the period ended September 30, 2019, 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></div><div><br></div><div style="text-align: justify;"><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="zdc19af720b5f42d097c56cb2d864b779"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman'; 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></div><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="zcb9503f2f4114296819162727eff9cd5"><tr><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><a name="z67c7d4b1a5524f7095e3a56b8ca645e7"><!--Anchor--></a>Dated: November 6, 2019</div></td><td style="width: 2%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 2%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 49%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">/s/ STANLEY T. CROOKE</div></td><td style="width: 2%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 49%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div></td></tr><tr><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Stanley T. Crooke, M.D., Ph.D.</div></td><td style="width: 2%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Elizabeth L. Hougen</div></td></tr><tr><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 2%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div></td><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Chief Financial Officer</div></td></tr></table><div><br></div><div style="text-align: justify; text-indent: 36pt; color: #000000; font-family: 'Times New Roman'; 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; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;"><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>8
<FILENAME>ions-20190930.xsd
<DESCRIPTION>XBRL TAXONOMY EXTENSION SCHEMA
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 6.2.0.0 Broadridge-->
<xs:schema targetNamespace="http://isispharm.com/20190930" elementFormDefault="qualified" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:ions="http://isispharm.com/20190930" 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/2019-01-31" xmlns:invest="http://xbrl.sec.gov/invest/2013-01-31" xmlns:srt-types="http://fasb.org/srt-types/2019-01-31" xmlns:num="http://www.xbrl.org/dtr/type/numeric" xmlns:nonnum="http://www.xbrl.org/dtr/type/non-numeric" xmlns:dei="http://xbrl.sec.gov/dei/2019-01-31">
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xlink:type="simple" xlink:href="ions-20190930_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-20190930_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-20190930_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-20190930_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://isispharm.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://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited" id="CondensedConsolidatedBalanceSheetsUnaudited">
        <link:definition>010000 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited)</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://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical" id="CondensedConsolidatedBalanceSheetsUnauditedParenthetical">
        <!--Parent Role: CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited)-->
        <link:definition>010100 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) (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://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited" id="CondensedConsolidatedStatementsOfOperationsUnaudited">
        <link:definition>020000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited)</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://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" id="CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited">
        <link:definition>030000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Unaudited)</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://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited" id="CondensedConsolidatedStatementsOfStockholdersEquityUnaudited">
        <link:definition>040000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited)</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://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited" id="CondensedConsolidatedStatementsOfCashFlowsUnaudited">
        <link:definition>050000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited)</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://isispharm.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://isispharm.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://isispharm.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://isispharm.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://isispharm.com/role/OperatingLeases" id="OperatingLeases">
        <link:definition>060500 - Disclosure - Operating Leases</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://isispharm.com/role/IncomeTaxes" id="IncomeTaxes">
        <link:definition>060600 - 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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements" id="CollaborativeArrangementsAndLicensingAgreements">
        <link:definition>060700 - 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://isispharm.com/role/SegmentInformation" id="SegmentInformation">
        <link:definition>060800 - Disclosure - Segment 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://isispharm.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://isispharm.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://isispharm.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://isispharm.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://isispharm.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://isispharm.com/role/OperatingLeasesTables" id="OperatingLeasesTables">
        <!--Parent Role: Operating Leases-->
        <link:definition>080500 - Disclosure - Operating Leases (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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" id="CollaborativeArrangementsAndLicensingAgreementsTables">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>080700 - 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://isispharm.com/role/SegmentInformationTables" id="SegmentInformationTables">
        <!--Parent Role: Segment Information-->
        <link:definition>080800 - Disclosure - Segment Information (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://isispharm.com/role/BasisOfPresentationDetails" id="BasisOfPresentationDetails">
        <!--Parent Role: Basis of Presentation-->
        <link:definition>090100 - Disclosure - Basis of Presentation (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://isispharm.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://isispharm.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://isispharm.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://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails" id="SignificantAccountingPoliciesCostOfProductsSoldDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090206 - Disclosure - Significant Accounting Policies, Cost of Products Sold (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://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails" id="SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090208 - Disclosure - Significant Accounting Policies, Noncontrolling Interest in Akcea (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://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" id="SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090210 - 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://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails" id="SignificantAccountingPoliciesInventoryValuationDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090212 - 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://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails" id="SignificantAccountingPoliciesLeasesDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090214 - 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://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" id="SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090216 - Disclosure - Significant Accounting Policies, Basic and Diluted Net Income (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://isispharm.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://isispharm.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://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails" id="SignificantAccountingPoliciesShareRepurchaseProgramDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090222 - Disclosure - Significant Accounting Policies, Share Repurchase Program (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://isispharm.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://isispharm.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://isispharm.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://isispharm.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://isispharm.com/role/OperatingLeasesDetails" id="OperatingLeasesDetails">
        <!--Parent Role: Operating Leases-->
        <link:definition>090500 - Disclosure - Operating 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://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2" id="OtherObligationsOperatingLeasesDetailsCalc2">
        <!--Parent Role: Operating Leases (Details)-->
        <link:definition>090502 - Disclosure - Other Obligations, Operating Leases (Details) Calc 2</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://isispharm.com/role/IncomeTaxesDetails" id="IncomeTaxesDetails">
        <!--Parent Role: Income Taxes-->
        <link:definition>090600 - 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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails" id="CollaborativeArrangementsAndLicensingAgreementsBiogenDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090700 - Disclosure - Collaborative Arrangements and Licensing Agreements, Biogen (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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails" id="CollaborativeArrangementsAndLicensingAgreementsBayerDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090706 - Disclosure - Collaborative Arrangements and Licensing Agreements, Bayer (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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails" id="CollaborativeArrangementsAndLicensingAgreementsGskDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090708 - Disclosure - Collaborative Arrangements and Licensing Agreements, GSK (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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails" id="CollaborativeArrangementsAndLicensingAgreementsRocheDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090710 - Disclosure - Collaborative Arrangements and Licensing Agreements, Roche (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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" id="CollaborativeArrangementsAndLicensingAgreementsNovartisDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090712 - Disclosure - Collaborative Arrangements and Licensing Agreements, Novartis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails" id="CollaborativeArrangementsAndLicensingAgreementsPfizerDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090716 - Disclosure - Collaborative Arrangements and Licensing Agreements, Pfizer (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://isispharm.com/role/SegmentInformationDetails" id="SegmentInformationDetails">
        <!--Parent Role: Segment Information-->
        <link:definition>090800 - Disclosure - 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>
    </xs:appinfo>
  </xs:annotation>
  <xs:import namespace="http://fasb.org/us-gaap/2019-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/dei/2019-01-31" schemaLocation="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/invest/2013-01-31" schemaLocation="https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/country/2017-01-31" schemaLocation="https://xbrl.sec.gov/country/2017/country-2017-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/currency/2019-01-31" schemaLocation="https://xbrl.sec.gov/currency/2019/currency-2019-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/exch/2019-01-31" schemaLocation="https://xbrl.sec.gov/exch/2019/exch-2019-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/naics/2017-01-31" schemaLocation="https://xbrl.sec.gov/naics/2017/naics-2017-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/sic/2011-01-31" schemaLocation="https://xbrl.sec.gov/sic/2011/sic-2011-01-31.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/2018-01-31" schemaLocation="https://xbrl.sec.gov/stpr/2018/stpr-2018-01-31.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://www.xbrl.org/dtr/type/non-numeric" schemaLocation="http://www.xbrl.org/dtr/type/nonNumeric-2009-12-16.xsd" />
  <xs:import namespace="http://www.xbrl.org/dtr/type/numeric" schemaLocation="http://www.xbrl.org/dtr/type/numeric-2009-12-16.xsd" />
  <xs:import namespace="http://fasb.org/us-types/2019-01-31" schemaLocation="http://xbrl.fasb.org/us-gaap/2019/elts/us-types-2019-01-31.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/2019-01-31" schemaLocation="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd" />
  <xs:import namespace="http://fasb.org/srt-types/2019-01-31" schemaLocation="http://xbrl.fasb.org/srt/2019/elts/srt-types-2019-01-31.xsd" />
  <xs:element name="LongTermObligationsNoncurrent" id="ions_LongTermObligationsNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="CashCashEquivalentsAndInvestmentsPolicyTextBlock" id="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ShareBasedCompensationTable" id="ions_ShareBasedCompensationTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ShareBasedCompensationLineItems" id="ions_ShareBasedCompensationLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="AkceaTherapeuticsIncMember" id="ions_AkceaTherapeuticsIncMember" type="nonnum: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="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" type="num: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="ConvertibleSeniorNotes1PercentMember" id="ions_ConvertibleSeniorNotes1PercentMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ResearchDevelopmentAndPatentMember" id="ions_ResearchDevelopmentAndPatentMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="EquityIncentivePlan2011Member" id="ions_EquityIncentivePlan2011Member" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="BoardOfDirectorStockOptionMember" id="ions_BoardOfDirectorStockOptionMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="BoardOfDirectorsMember" id="ions_BoardOfDirectorsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="EmployeeMember" id="ions_EmployeeMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfExecutiveOfficersTerminatingEmployment" id="ions_NumberOfExecutiveOfficersTerminatingEmployment" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" 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="CommercialMember" id="ions_CommercialMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="SPINRAZARoyaltiesMember" id="ions_SPINRAZARoyaltiesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="LicensingAndOtherRoyaltiesMember" id="ions_LicensingAndOtherRoyaltiesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" type="nonnum: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="IncreaseDecreaseInAccruedAndDeferredLiabilities" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="PaymentsToAcquireLicensesAndOtherAssets" id="ions_PaymentsToAcquireLicensesAndOtherAssets" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" />
  <xs:element name="OperatingLeaseRightOfUseAssetAmortization" id="ions_OperatingLeaseRightOfUseAssetAmortization" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="BiogenIncMember" id="ions_BiogenIncMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NovartisInternationalAGMember" id="ions_NovartisInternationalAGMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementsAndLicensingAgreementsAbstract" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="SecuritiesWithMaturityOfOneYearOrLessMember" id="ions_SecuritiesWithMaturityOfOneYearOrLessMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="SecuritiesWithMaturityOfMoreThanOneYearMember" id="ions_SecuritiesWithMaturityOfMoreThanOneYearMember" type="nonnum: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="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="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" type="xbrli:integerItemType" 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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" type="nonnum: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="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementsAndLicensingAgreementsBayerMember" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="IONISLRRK2Member" id="ions_IONISLRRK2Member" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfDrugsCurrentlyBeingAdvanced" id="ions_NumberOfDrugsCurrentlyBeingAdvanced" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementAbstract" id="ions_CollaborativeArrangementAndLicensingAgreementAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NextPotentialMilestonePayment" id="ions_NextPotentialMilestonePayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <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="CostOfProductsSoldPreviouslyRecognized" id="ions_CostOfProductsSoldPreviouslyRecognized" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="IonisCoreMember" id="ions_IonisCoreMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="AkceaTherapeuticsMember" id="ions_AkceaTherapeuticsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="WeightedAverageNumberOfSharesOwnedInSubsidiary" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="MilestonePaymentEarned" id="ions_MilestonePaymentEarned" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" />
  <xs:element name="ReceiptOfSharesInSubsidiary" id="ions_ReceiptOfSharesInSubsidiary" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="SublicenseFeePaidForLicenseOfDrug" id="ions_SublicenseFeePaidForLicenseOfDrug" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" />
  <xs:element name="AKCEAAPOALMember" id="ions_AKCEAAPOALMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfCollaborationAgreements" id="ions_NumberOfCollaborationAgreements" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="IonisHttMember" id="ions_IonisHttMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementsAndLicensingAgreementsRocheMember" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="PaymentsIncludedInTransactionPriceForPerformanceObligation" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="MilestonePaymentsReceived" id="ions_MilestonePaymentsReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="UpfrontPaymentReceivedIncludingPurchaseOfStock" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="IONISMAPTMember" id="ions_IONISMAPTMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" id="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="NumberOfMilestonePaymentsAchieved" id="ions_NumberOfMilestonePaymentsAchieved" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="NumberOfNewTargetsAdvanced" id="ions_NumberOfNewTargetsAdvanced" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ResearchAndDevelopmentServicesMember" id="ions_ResearchAndDevelopmentServicesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" type="xbrli:stringItemType" 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="LesseeOperatingLeasePeriodOfFreeRent" id="ions_LesseeOperatingLeasePeriodOfFreeRent" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="LesseeOperatingLeaseAllowanceForTenantImprovements" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="OfficeSpaceForCorporateHeadquartersMember" id="ions_OfficeSpaceForCorporateHeadquartersMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" id="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" id="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="LesseeOperatingLeaseInformationTableTextBlock" id="ions_LesseeOperatingLeaseInformationTableTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="UpfrontLicenseFeeToBeReceived" id="ions_UpfrontLicenseFeeToBeReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="RoyaltyPercentageReceivedOnNetSalesOfDrug" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug" type="num:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
</xs:schema>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.CAL
<SEQUENCE>9
<FILENAME>ions-20190930_cal.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION CALCULATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 6.2.0.0 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://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2" xlink:type="simple" xlink:href="ions-20190930.xsd#OtherObligationsOperatingLeasesDetailsCalc2" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeasesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeasesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurementsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsInvestmentsTemporarilyImpairedDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsSummaryOfInvestmentsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfCashFlowsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfOperationsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedBalanceSheetsUnaudited" />
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Assets" xlink:label="Assets" xlink:title="Assets" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="AssetsCurrent" xlink:title="AssetsCurrent" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:label="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:title="DeferredTaxAssetsLiabilitiesNetNoncurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Assets" xlink:to="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:title="calculation: Assets to DeferredTaxAssetsLiabilitiesNetNoncurrent" order="5.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:label="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="LongTermDebtAndCapitalLeaseObligationsCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="calculation: LiabilitiesCurrent to LongTermDebtAndCapitalLeaseObligationsCurrent" order="5.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_LongTermObligationsNoncurrent" xlink:label="LongTermObligationsNoncurrent" xlink:title="LongTermObligationsNoncurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Liabilities" xlink:to="LongTermObligationsNoncurrent" xlink:title="calculation: Liabilities to LongTermObligationsNoncurrent" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterest" xlink:label="MinorityInterest" xlink:title="MinorityInterest" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="MinorityInterest" xlink:title="calculation: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to MinorityInterest" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="StockholdersEquity" xlink:title="calculation: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to StockholdersEquity" order="0.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="calculation: LiabilitiesAndStockholdersEquity to StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" order="2.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ProfitLoss" xlink:to="IncomeTaxExpenseBenefit" xlink:title="calculation: ProfitLoss to IncomeTaxExpenseBenefit" order="1.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:to="OtherNonoperatingIncomeExpense" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments to OtherNonoperatingIncomeExpense" order="7.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:to="InvestmentIncomeNet" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments to InvestmentIncomeNet" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:to="InterestExpense" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments to InterestExpense" order="4.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:to="OperatingIncomeLoss" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments to OperatingIncomeLoss" order="1.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ProfitLoss" xlink:to="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="calculation: ProfitLoss to IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" order="0.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetIncomeLoss" xlink:to="ProfitLoss" xlink:title="calculation: NetIncomeLoss to ProfitLoss" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAttributableToNoncontrollingInterest" xlink:label="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="NetIncomeLossAttributableToNoncontrollingInterest" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetIncomeLoss" xlink:to="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="calculation: NetIncomeLoss to NetIncomeLossAttributableToNoncontrollingInterest" order="1.0" weight="-1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:label="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:title="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:title="calculation: ComprehensiveIncomeNetOfTax to ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" order="1.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:label="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:title="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:to="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="calculation: ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest to OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:to="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="calculation: ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest to OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:to="ProfitLoss" xlink:title="calculation: ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest to ProfitLoss" order="0.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:title="calculation: ComprehensiveIncomeNetOfTax to ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" order="0.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="ProceedsFromIssuanceOfCommonStock" xlink:title="ProceedsFromIssuanceOfCommonStock" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="ProceedsFromIssuanceOfCommonStock" xlink:title="calculation: NetCashProvidedByUsedInFinancingActivities to ProceedsFromIssuanceOfCommonStock" order="12.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:label="RepaymentsOfLongTermDebt" xlink:title="RepaymentsOfLongTermDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="RepaymentsOfLongTermDebt" xlink:title="calculation: NetCashProvidedByUsedInFinancingActivities to RepaymentsOfLongTermDebt" order="13.0" weight="-1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="NetCashProvidedByUsedInFinancingActivities" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect to NetCashProvidedByUsedInFinancingActivities" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="NetCashProvidedByUsedInInvestingActivities" xlink:title="NetCashProvidedByUsedInInvestingActivities" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_PaymentsToAcquireLicensesAndOtherAssets" xlink:label="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="PaymentsToAcquireLicensesAndOtherAssets" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="calculation: NetCashProvidedByUsedInInvestingActivities to PaymentsToAcquireLicensesAndOtherAssets" order="5.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="NetCashProvidedByUsedInInvestingActivities" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect to NetCashProvidedByUsedInInvestingActivities" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfDebtDiscountPremium" xlink:label="AmortizationOfDebtDiscountPremium" xlink:title="AmortizationOfDebtDiscountPremium" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="AmortizationOfDebtDiscountPremium" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to AmortizationOfDebtDiscountPremium" order="6.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetImpairmentCharges" xlink:label="AssetImpairmentCharges" xlink:title="AssetImpairmentCharges" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="AssetImpairmentCharges" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to AssetImpairmentCharges" order="12.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="ProfitLoss" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to ProfitLoss" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="16.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="18.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="15.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="21.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="17.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="19.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:label="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="IncreaseDecreaseInAccruedAndDeferredLiabilities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInAccruedAndDeferredLiabilities" order="20.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:label="DeferredIncomeTaxExpenseBenefit" xlink:title="DeferredIncomeTaxExpenseBenefit" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="DeferredIncomeTaxExpenseBenefit" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to DeferredIncomeTaxExpenseBenefit" order="14.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OperatingLeaseRightOfUseAssetAmortization" xlink:label="OperatingLeaseRightOfUseAssetAmortization" xlink:title="OperatingLeaseRightOfUseAssetAmortization" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="OperatingLeaseRightOfUseAssetAmortization" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to OperatingLeaseRightOfUseAssetAmortization" order="2.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="NetCashProvidedByUsedInOperatingActivities" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect to NetCashProvidedByUsedInOperatingActivities" order="2.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="WeightedAverageNumberOfDilutedSharesOutstanding" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="calculation: WeightedAverageNumberOfDilutedSharesOutstanding to IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="calculation: WeightedAverageNumberOfDilutedSharesOutstanding to IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="WeightedAverageNumberOfSharesOutstandingBasic" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="calculation: WeightedAverageNumberOfDilutedSharesOutstanding to WeightedAverageNumberOfSharesOutstandingBasic" order="0.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:title="calculation: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" order="3.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="calculation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="calculation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="calculation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss to AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="calculation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" order="2.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="AssetsFairValueDisclosure" xlink:title="AssetsFairValueDisclosure" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecurities" xlink:label="AvailableForSaleSecurities" xlink:title="AvailableForSaleSecurities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsFairValueDisclosure" xlink:to="AvailableForSaleSecurities" xlink:title="calculation: AssetsFairValueDisclosure to AvailableForSaleSecurities" order="1.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/OperatingLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityPaymentsDueYearFour" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityPaymentsDueYearThree" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityPaymentsDueYearFive" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" order="5.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="OperatingLeaseLiability" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to OperatingLeaseLiability" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="calculation: LesseeOperatingLeaseLiabilityPaymentsDue to LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" order="0.0" weight="1.0" />
  </link:calculationLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.DEF
<SEQUENCE>10
<FILENAME>ions-20190930_def.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION DEFINITION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 6.2.0.0 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://isispharm.com/role/SegmentInformationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SegmentInformationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsPfizerDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsRocheDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsGskDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsBayerDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsBiogenDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/IncomeTaxesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#IncomeTaxesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2" xlink:type="simple" xlink:href="ions-20190930.xsd#OtherObligationsOperatingLeasesDetailsCalc2" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeasesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeasesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurementsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsInvestmentsTemporarilyImpairedDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsSummaryOfInvestmentsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesShareRepurchaseProgramDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesSegmentInformationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesLeasesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesInventoryValuationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesCostOfProductsSoldDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesDeferredRevenueDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesContractsReceivableDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesRevenueRecognitionDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/BasisOfPresentationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#BasisOfPresentationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SegmentInformationTables" xlink:type="simple" xlink:href="ions-20190930.xsd#SegmentInformationTables" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsTables" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeasesTables" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeasesTables" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurementsTables" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurementsTables" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsTables" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsTables" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesTables" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesTables" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesPolicies" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesPolicies" />
  <link:roleRef roleURI="http://isispharm.com/role/BasisOfPresentationPolicies" xlink:type="simple" xlink:href="ions-20190930.xsd#BasisOfPresentationPolicies" />
  <link:roleRef roleURI="http://isispharm.com/role/SegmentInformation" xlink:type="simple" xlink:href="ions-20190930.xsd#SegmentInformation" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreements" />
  <link:roleRef roleURI="http://isispharm.com/role/IncomeTaxes" xlink:type="simple" xlink:href="ions-20190930.xsd#IncomeTaxes" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeases" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeases" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurements" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurements" />
  <link:roleRef roleURI="http://isispharm.com/role/Investments" xlink:type="simple" xlink:href="ions-20190930.xsd#Investments" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPolicies" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPolicies" />
  <link:roleRef roleURI="http://isispharm.com/role/BasisOfPresentation" xlink:type="simple" xlink:href="ions-20190930.xsd#BasisOfPresentation" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfCashFlowsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfStockholdersEquityUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfOperationsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedBalanceSheetsUnauditedParenthetical" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedBalanceSheetsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/DocumentAndEntityInformation" xlink:type="simple" xlink:href="ions-20190930.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://isispharm.com/role/DocumentAndEntityInformation" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="definition: StatementLineItems to IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ProfitLoss" xlink:title="definition: StatementLineItems to ProfitLoss" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAttributableToNoncontrollingInterest" xlink:label="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="NetIncomeLossAttributableToNoncontrollingInterest" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="definition: StatementLineItems to NetIncomeLossAttributableToNoncontrollingInterest" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="14.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="15.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="16.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="17.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="18.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="19.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="20.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="21.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="22.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.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-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="StockIssuedDuringPeriodValueNewIssues" xlink:title="StockIssuedDuringPeriodValueNewIssues" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockIssuedDuringPeriodValueNewIssues" xlink:title="definition: StatementLineItems to StockIssuedDuringPeriodValueNewIssues" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="StockIssuedDuringPeriodSharesNewIssues" xlink:title="StockIssuedDuringPeriodSharesNewIssues" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockIssuedDuringPeriodSharesNewIssues" xlink:title="definition: StatementLineItems to StockIssuedDuringPeriodSharesNewIssues" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestPeriodIncreaseDecrease" xlink:label="MinorityInterestPeriodIncreaseDecrease" xlink:title="MinorityInterestPeriodIncreaseDecrease" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="MinorityInterestPeriodIncreaseDecrease" xlink:title="definition: StatementLineItems to MinorityInterestPeriodIncreaseDecrease" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="15.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ParentMember" xlink:label="ParentMember" xlink:title="ParentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityComponentDomain" xlink:to="ParentMember" xlink:title="definition: EquityComponentDomain to ParentMember" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NoncontrollingInterestMember" xlink:label="NoncontrollingInterestMember" xlink:title="NoncontrollingInterestMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityComponentDomain" xlink:to="NoncontrollingInterestMember" xlink:title="definition: EquityComponentDomain to NoncontrollingInterestMember" order="6.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="definition: StatementLineItems to NetCashProvidedByUsedInOperatingActivitiesAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="definition: StatementLineItems to NetCashProvidedByUsedInInvestingActivitiesAbstract" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInFinancingActivitiesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="definition: StatementLineItems to NetCashProvidedByUsedInFinancingActivitiesAbstract" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:title="definition: StatementLineItems to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="definition: StatementLineItems to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SupplementalCashFlowInformationAbstract" xlink:label="SupplementalCashFlowInformationAbstract" xlink:title="SupplementalCashFlowInformationAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="SupplementalCashFlowInformationAbstract" xlink:title="definition: StatementLineItems to SupplementalCashFlowInformationAbstract" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:label="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="definition: StatementLineItems to CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:label="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="definition: StatementLineItems to RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NonCashCapitalAndPatentExpenditures" xlink:title="definition: StatementLineItems to NonCashCapitalAndPatentExpenditures" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CapitalExpendituresIncurredButNotYetPaid" xlink:label="CapitalExpendituresIncurredButNotYetPaid" xlink:title="CapitalExpendituresIncurredButNotYetPaid" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CapitalExpendituresIncurredButNotYetPaid" xlink:title="definition: StatementLineItems to CapitalExpendituresIncurredButNotYetPaid" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="InterestPaidNet" xlink:title="definition: StatementLineItems to InterestPaidNet" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxesPaid" xlink:label="IncomeTaxesPaid" xlink:title="IncomeTaxesPaid" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncomeTaxesPaid" xlink:title="definition: StatementLineItems to IncomeTaxesPaid" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="definition: StatementLineItems to ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="definition: StatementLineItems to PaymentsRelatedToTaxWithholdingForShareBasedCompensation" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="ProceedsFromIssuanceOfCommonStock" xlink:title="ProceedsFromIssuanceOfCommonStock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ProceedsFromIssuanceOfCommonStock" xlink:title="definition: StatementLineItems to ProceedsFromIssuanceOfCommonStock" order="15.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:label="RepaymentsOfLongTermDebt" xlink:title="RepaymentsOfLongTermDebt" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="RepaymentsOfLongTermDebt" xlink:title="definition: StatementLineItems to RepaymentsOfLongTermDebt" order="16.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetCashProvidedByUsedInFinancingActivities" xlink:title="definition: StatementLineItems to NetCashProvidedByUsedInFinancingActivities" order="17.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="definition: StatementLineItems to PaymentsToAcquireAvailableForSaleSecuritiesDebt" order="18.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="definition: StatementLineItems to ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" order="19.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="definition: StatementLineItems to PaymentsToAcquirePropertyPlantAndEquipment" order="20.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_PaymentsToAcquireLicensesAndOtherAssets" xlink:label="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="PaymentsToAcquireLicensesAndOtherAssets" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="definition: StatementLineItems to PaymentsToAcquireLicensesAndOtherAssets" order="21.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="NetCashProvidedByUsedInInvestingActivities" xlink:title="NetCashProvidedByUsedInInvestingActivities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetCashProvidedByUsedInInvestingActivities" xlink:title="definition: StatementLineItems to NetCashProvidedByUsedInInvestingActivities" order="22.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ProfitLoss" xlink:title="definition: StatementLineItems to ProfitLoss" order="23.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="definition: StatementLineItems to AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" order="24.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetCashProvidedByUsedInOperatingActivities" xlink:title="definition: StatementLineItems to NetCashProvidedByUsedInOperatingActivities" order="25.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_Depreciation" xlink:label="Depreciation" xlink:title="Depreciation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="Depreciation" xlink:title="definition: StatementLineItems to Depreciation" order="26.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OperatingLeaseRightOfUseAssetAmortization" xlink:label="OperatingLeaseRightOfUseAssetAmortization" xlink:title="OperatingLeaseRightOfUseAssetAmortization" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OperatingLeaseRightOfUseAssetAmortization" xlink:title="definition: StatementLineItems to OperatingLeaseRightOfUseAssetAmortization" order="27.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AmortizationOfIntangibleAssets" xlink:title="definition: StatementLineItems to AmortizationOfIntangibleAssets" order="28.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:label="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="AccretionAmortizationOfDiscountsAndPremiumsInvestments" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="definition: StatementLineItems to AccretionAmortizationOfDiscountsAndPremiumsInvestments" order="29.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="AmortizationOfFinancingCosts" xlink:title="AmortizationOfFinancingCosts" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AmortizationOfFinancingCosts" xlink:title="definition: StatementLineItems to AmortizationOfFinancingCosts" order="30.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfDebtDiscountPremium" xlink:label="AmortizationOfDebtDiscountPremium" xlink:title="AmortizationOfDebtDiscountPremium" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AmortizationOfDebtDiscountPremium" xlink:title="definition: StatementLineItems to AmortizationOfDebtDiscountPremium" order="31.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ShareBasedCompensation" xlink:title="definition: StatementLineItems to ShareBasedCompensation" order="32.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetImpairmentCharges" xlink:label="AssetImpairmentCharges" xlink:title="AssetImpairmentCharges" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AssetImpairmentCharges" xlink:title="definition: StatementLineItems to AssetImpairmentCharges" order="33.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:label="DeferredIncomeTaxExpenseBenefit" xlink:title="DeferredIncomeTaxExpenseBenefit" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="DeferredIncomeTaxExpenseBenefit" xlink:title="definition: StatementLineItems to DeferredIncomeTaxExpenseBenefit" order="34.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="definition: StatementLineItems to IncreaseDecreaseInOperatingCapitalAbstract" order="35.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerAsset" xlink:label="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="IncreaseDecreaseInContractWithCustomerAsset" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="definition: StatementLineItems to IncreaseDecreaseInContractWithCustomerAsset" order="36.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="IncreaseDecreaseInInventories" xlink:title="IncreaseDecreaseInInventories" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInInventories" xlink:title="definition: StatementLineItems to IncreaseDecreaseInInventories" order="37.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInOtherOperatingAssets" xlink:title="definition: StatementLineItems to IncreaseDecreaseInOtherOperatingAssets" order="38.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="IncreaseDecreaseInAccountsPayable" xlink:title="IncreaseDecreaseInAccountsPayable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInAccountsPayable" xlink:title="definition: StatementLineItems to IncreaseDecreaseInAccountsPayable" order="39.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="definition: StatementLineItems to IncreaseDecreaseInOtherEmployeeRelatedLiabilities" order="40.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:label="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="IncreaseDecreaseInAccruedAndDeferredLiabilities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="definition: StatementLineItems to IncreaseDecreaseInAccruedAndDeferredLiabilities" order="41.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="IncreaseDecreaseInContractWithCustomerLiability" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="definition: StatementLineItems to IncreaseDecreaseInContractWithCustomerLiability" order="42.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="43.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="StatementTable" xlink:to="MajorCustomersAxis" xlink:title="definition: StatementTable to MajorCustomersAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.xsd#ions_NovartisInternationalAGMember" xlink:label="NovartisInternationalAGMember" xlink:title="NovartisInternationalAGMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="NameOfMajorCustomerDomain" xlink:to="NovartisInternationalAGMember" xlink:title="definition: NameOfMajorCustomerDomain to NovartisInternationalAGMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/BasisOfPresentation" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPolicies" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/Investments" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/FairValueMeasurements" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/OperatingLeases" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/IncomeTaxes" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SegmentInformation" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/BasisOfPresentationPolicies" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesPolicies" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesTables">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ShareBasedCompensationLineItems" xlink:label="ShareBasedCompensationLineItems" xlink:title="ShareBasedCompensationLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationLineItems" xlink:to="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="definition: ShareBasedCompensationLineItems to ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationLineItems" xlink:to="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="definition: ShareBasedCompensationLineItems to ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ShareBasedCompensationTable" xlink:label="ShareBasedCompensationTable" xlink:title="ShareBasedCompensationTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ShareBasedCompensationLineItems" xlink:to="ShareBasedCompensationTable" xlink:title="definition: ShareBasedCompensationLineItems to ShareBasedCompensationTable" order="3.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ShareBasedCompensationTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="definition: ShareBasedCompensationTable to ConsolidatedEntitiesAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain_2" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain_2" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/FairValueMeasurementsTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/OperatingLeasesTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:label="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:title="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:title="definition: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="definition: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" order="2.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="TypeOfArrangementAxis" xlink:title="definition: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to TypeOfArrangementAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsBiogenMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsRocheMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" order="4.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SegmentInformationTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/BasisOfPresentationDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:label="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:title="ProceedsFromIssuanceOrSaleOfEquityAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:title="definition: MinorityInterestLineItems to ProceedsFromIssuanceOrSaleOfEquityAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="MinorityInterestOwnershipPercentageByParent" xlink:title="definition: MinorityInterestLineItems to MinorityInterestOwnershipPercentageByParent" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="definition: MinorityInterestLineItems to ReceiptOfSharesInSubsidiary" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="MinorityInterestLineItems" xlink:to="MinorityInterestTable" xlink:title="definition: MinorityInterestLineItems to MinorityInterestTable" order="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="MinorityInterestTable" xlink:to="OwnershipAxis" xlink:title="definition: MinorityInterestTable to OwnershipAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="definition: OwnershipAxis to OwnershipDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain_2" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain_2" xlink:title="definition: OwnershipAxis to OwnershipDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: OwnershipDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="MinorityInterestTable" xlink:to="StatementScenarioAxis" xlink:title="definition: MinorityInterestTable to StatementScenarioAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain" xlink:title="definition: StatementScenarioAxis to ScenarioUnspecifiedDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain_2" xlink:title="ScenarioUnspecifiedDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain_2" xlink:title="definition: StatementScenarioAxis to ScenarioUnspecifiedDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScenarioUnspecifiedDomain" xlink:to="ScenarioForecastMember" xlink:title="definition: ScenarioUnspecifiedDomain to ScenarioForecastMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:label="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="definition: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="7.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="8.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBayerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsBayerMember" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsBayerMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsBayerMember to CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.xsd#ions_IONISLRRK2Member" xlink:label="IONISLRRK2Member" xlink:title="IONISLRRK2Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="IONISLRRK2Member" xlink:title="definition: ProductsAndServicesDomain to IONISLRRK2Member" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="ProductsAndServicesDomain" xlink:to="LicensingAndOtherRoyaltiesMember" xlink:title="definition: ProductsAndServicesDomain to LicensingAndOtherRoyaltiesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.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://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NoncontrollingInterestAbstract" xlink:label="NoncontrollingInterestAbstract" xlink:title="NoncontrollingInterestAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="NoncontrollingInterestAbstract" xlink:title="definition: MinorityInterestLineItems to NoncontrollingInterestAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="MinorityInterestOwnershipPercentageByParent" xlink:title="definition: MinorityInterestLineItems to MinorityInterestOwnershipPercentageByParent" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="definition: MinorityInterestLineItems to ReceiptOfSharesInSubsidiary" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="MinorityInterestLineItems" xlink:to="MinorityInterestTable" xlink:title="definition: MinorityInterestLineItems to MinorityInterestTable" order="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="MinorityInterestTable" xlink:to="OwnershipAxis" xlink:title="definition: MinorityInterestTable to OwnershipAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="definition: OwnershipAxis to OwnershipDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain_2" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain_2" xlink:title="definition: OwnershipAxis to OwnershipDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: OwnershipDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="MinorityInterestTable" xlink:to="StatementScenarioAxis" xlink:title="definition: MinorityInterestTable to StatementScenarioAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain" xlink:title="definition: StatementScenarioAxis to ScenarioUnspecifiedDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain_2" xlink:title="ScenarioUnspecifiedDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain_2" xlink:title="definition: StatementScenarioAxis to ScenarioUnspecifiedDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScenarioUnspecifiedDomain" xlink:to="ScenarioForecastMember" xlink:title="definition: ScenarioUnspecifiedDomain to ScenarioForecastMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:label="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:title="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="LesseeDisclosureAbstract" xlink:title="definition: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems to LesseeDisclosureAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="OperatingLeaseRightOfUseAsset" xlink:title="definition: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems to OperatingLeaseRightOfUseAsset" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="OperatingLeaseLiability" xlink:title="definition: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems to OperatingLeaseLiability" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="OperatingLeaseLiabilityCurrent" xlink:title="definition: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems to OperatingLeaseLiabilityCurrent" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:label="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:title="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:title="definition: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems to NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" order="5.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="AdjustmentsForNewAccountingPronouncementsAxis" xlink:title="AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="AdjustmentsForNewAccountingPronouncementsAxis" xlink:title="definition: NewAccountingPronouncementsOrChangeInAccountingPrincipleTable to AdjustmentsForNewAccountingPronouncementsAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="TypeOfAdoptionMember" xlink:title="TypeOfAdoptionMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="TypeOfAdoptionMember" xlink:title="definition: AdjustmentsForNewAccountingPronouncementsAxis to TypeOfAdoptionMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="TypeOfAdoptionMember_2" xlink:title="TypeOfAdoptionMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="TypeOfAdoptionMember_2" xlink:title="definition: AdjustmentsForNewAccountingPronouncementsAxis to TypeOfAdoptionMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201602Member" xlink:label="AccountingStandardsUpdate201602Member" xlink:title="AccountingStandardsUpdate201602Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TypeOfAdoptionMember" xlink:to="AccountingStandardsUpdate201602Member" xlink:title="definition: TypeOfAdoptionMember to AccountingStandardsUpdate201602Member" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EarningsPerShareBasicLineItems" xlink:label="EarningsPerShareBasicLineItems" xlink:title="EarningsPerShareBasicLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:label="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="WeightedAverageNumberOfSharesOwnedInSubsidiary" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="definition: EarningsPerShareBasicLineItems to WeightedAverageNumberOfSharesOwnedInSubsidiary" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicLineItems" xlink:to="NetIncomeLoss" xlink:title="definition: EarningsPerShareBasicLineItems to NetIncomeLoss" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic" xlink:label="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:title="NetIncomeLossAvailableToCommonStockholdersBasic" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:title="definition: EarningsPerShareBasicLineItems to NetIncomeLossAvailableToCommonStockholdersBasic" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicLineItems" xlink:to="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="definition: EarningsPerShareBasicLineItems to WeightedAverageNumberOfSharesOutstandingBasic" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:label="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:title="NetIncomeLossAvailableToCommonStockholdersDiluted" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:title="definition: EarningsPerShareBasicLineItems to NetIncomeLossAvailableToCommonStockholdersDiluted" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="definition: EarningsPerShareBasicLineItems to IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="definition: EarningsPerShareBasicLineItems to IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicLineItems" xlink:to="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="definition: EarningsPerShareBasicLineItems to WeightedAverageNumberOfDilutedSharesOutstanding" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicLineItems" xlink:to="EarningsPerShareDiluted" xlink:title="definition: EarningsPerShareBasicLineItems to EarningsPerShareDiluted" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="OwnershipAxis" xlink:title="definition: ScheduleOfEarningsPerShareBasicByCommonClassTable to OwnershipAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="definition: OwnershipAxis to OwnershipDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain_2" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain_2" xlink:title="definition: OwnershipAxis to OwnershipDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: OwnershipDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="StatementClassOfStockAxis" xlink:title="StatementClassOfStockAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="StatementClassOfStockAxis" xlink:title="definition: ScheduleOfEarningsPerShareBasicByCommonClassTable to StatementClassOfStockAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:label="ClassOfStockDomain" xlink:title="ClassOfStockDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementClassOfStockAxis" xlink:to="ClassOfStockDomain" xlink:title="definition: StatementClassOfStockAxis to ClassOfStockDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:label="ClassOfStockDomain_2" xlink:title="ClassOfStockDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementClassOfStockAxis" xlink:to="ClassOfStockDomain_2" xlink:title="definition: StatementClassOfStockAxis to ClassOfStockDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConvertiblePreferredStockMember" xlink:label="ConvertiblePreferredStockMember" xlink:title="ConvertiblePreferredStockMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ClassOfStockDomain" xlink:to="ConvertiblePreferredStockMember" xlink:title="definition: ClassOfStockDomain to ConvertiblePreferredStockMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ClassOfStockDomain" xlink:to="CommonStockMember" xlink:title="definition: ClassOfStockDomain to CommonStockMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="StatementBusinessSegmentsAxis" xlink:title="definition: ScheduleOfEarningsPerShareBasicByCommonClassTable to StatementBusinessSegmentsAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain" xlink:title="SegmentDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementBusinessSegmentsAxis" xlink:to="SegmentDomain" xlink:title="definition: StatementBusinessSegmentsAxis to SegmentDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain_2" xlink:title="SegmentDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementBusinessSegmentsAxis" xlink:to="SegmentDomain_2" xlink:title="definition: StatementBusinessSegmentsAxis to SegmentDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="SegmentDomain" xlink:to="IonisCoreMember" xlink:title="definition: SegmentDomain to IonisCoreMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="AwardTypeAxis" xlink:title="definition: ScheduleOfEarningsPerShareBasicByCommonClassTable to AwardTypeAxis" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="RestrictedStockMember" xlink:title="RestrictedStockMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="RestrictedStockMember" xlink:title="definition: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to RestrictedStockMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_NumberOfExecutiveOfficersTerminatingEmployment" xlink:label="NumberOfExecutiveOfficersTerminatingEmployment" xlink:title="NumberOfExecutiveOfficersTerminatingEmployment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="NumberOfExecutiveOfficersTerminatingEmployment" xlink:title="definition: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to NumberOfExecutiveOfficersTerminatingEmployment" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="definition: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to ConsolidatedEntitiesAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain_2" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain_2" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="IncomeStatementLocationDomain" xlink:to="ResearchDevelopmentAndPatentMember" xlink:title="definition: IncomeStatementLocationDomain to ResearchDevelopmentAndPatentMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:label="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:title="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:label="CommonStockCapitalSharesReservedForFutureIssuance" xlink:title="CommonStockCapitalSharesReservedForFutureIssuance" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="CommonStockCapitalSharesReservedForFutureIssuance" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to CommonStockCapitalSharesReservedForFutureIssuance" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="8.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="14.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="15.0" t1:closed="true" t1:contextElement="segment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to ConsolidatedEntitiesAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="PlanNameAxis" xlink:title="PlanNameAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="PlanNameAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to PlanNameAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="PlanNameDomain" xlink:title="PlanNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="PlanNameAxis" xlink:to="PlanNameDomain" xlink:title="definition: PlanNameAxis to PlanNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="PlanNameDomain_2" xlink:title="PlanNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="PlanNameAxis" xlink:to="PlanNameDomain_2" xlink:title="definition: PlanNameAxis to PlanNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_EquityIncentivePlan2011Member" xlink:label="EquityIncentivePlan2011Member" xlink:title="EquityIncentivePlan2011Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PlanNameDomain" xlink:to="EquityIncentivePlan2011Member" xlink:title="definition: PlanNameDomain to EquityIncentivePlan2011Member" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_BoardOfDirectorStockOptionMember" xlink:label="BoardOfDirectorStockOptionMember" xlink:title="BoardOfDirectorStockOptionMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="BoardOfDirectorStockOptionMember" xlink:title="definition: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to BoardOfDirectorStockOptionMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="RelatedPartyTransactionsByRelatedPartyAxis" xlink:title="RelatedPartyTransactionsByRelatedPartyAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="RelatedPartyTransactionsByRelatedPartyAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to RelatedPartyTransactionsByRelatedPartyAxis" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:label="RelatedPartyDomain" xlink:title="RelatedPartyDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="RelatedPartyDomain" xlink:title="definition: RelatedPartyTransactionsByRelatedPartyAxis to RelatedPartyDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:label="RelatedPartyDomain_2" xlink:title="RelatedPartyDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="RelatedPartyDomain_2" xlink:title="definition: RelatedPartyTransactionsByRelatedPartyAxis to RelatedPartyDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_EmployeeMember" xlink:label="EmployeeMember" xlink:title="EmployeeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="RelatedPartyDomain" xlink:to="EmployeeMember" xlink:title="definition: RelatedPartyDomain to EmployeeMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_BoardOfDirectorsMember" xlink:label="BoardOfDirectorsMember" xlink:title="BoardOfDirectorsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="RelatedPartyDomain" xlink:to="BoardOfDirectorsMember" xlink:title="definition: RelatedPartyDomain to BoardOfDirectorsMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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-20190930.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-20190930.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-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="14.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="InvestmentTypeAxis" xlink:title="InvestmentTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InvestmentHoldingsTable" xlink:to="InvestmentTypeAxis" xlink:title="definition: InvestmentHoldingsTable to InvestmentTypeAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember" xlink:title="InvestmentTypeCategorizationMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="InvestmentTypeAxis" xlink:to="InvestmentTypeCategorizationMember" xlink:title="definition: InvestmentTypeAxis to InvestmentTypeCategorizationMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember_2" xlink:title="InvestmentTypeCategorizationMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="InvestmentTypeAxis" xlink:to="InvestmentTypeCategorizationMember_2" xlink:title="definition: InvestmentTypeAxis to InvestmentTypeCategorizationMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="InvestmentTypeCategorizationMember" xlink:to="DebtSecuritiesMember" xlink:title="definition: InvestmentTypeCategorizationMember to DebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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-20190930.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:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:label="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:title="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:title="definition: InvestmentHoldingsLineItems to AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="InvestmentTypeAxis" xlink:title="InvestmentTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InvestmentHoldingsTable" xlink:to="InvestmentTypeAxis" xlink:title="definition: InvestmentHoldingsTable to InvestmentTypeAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember" xlink:title="InvestmentTypeCategorizationMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="InvestmentTypeAxis" xlink:to="InvestmentTypeCategorizationMember" xlink:title="definition: InvestmentTypeAxis to InvestmentTypeCategorizationMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember_2" xlink:title="InvestmentTypeCategorizationMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="InvestmentTypeAxis" xlink:to="InvestmentTypeCategorizationMember_2" xlink:title="definition: InvestmentTypeAxis to InvestmentTypeCategorizationMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="InvestmentTypeCategorizationMember" xlink:to="DebtSecuritiesMember" xlink:title="definition: InvestmentTypeCategorizationMember to DebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecurities" xlink:label="AvailableForSaleSecurities" xlink:title="AvailableForSaleSecurities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="AvailableForSaleSecurities" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to AvailableForSaleSecurities" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/OperatingLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:label="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="LesseeOperatingLeaseRenewalTerm" xlink:title="LesseeOperatingLeaseRenewalTerm" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseRenewalTerm" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseRenewalTerm" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseTermOfContract" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseTermOfContract" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:label="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="LesseeOperatingLeasePeriodOfFreeRent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeasePeriodOfFreeRent" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:label="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="LesseeOperatingLeaseAllowanceForTenantImprovements" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseAllowanceForTenantImprovements" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:label="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseRightOfUseAsset" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseRightOfUseAsset" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseLiability" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseLiability" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:label="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="OperatingLeaseWeightedAverageRemainingLeaseTerm1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseWeightedAverageRemainingLeaseTerm1" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent" xlink:label="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="OperatingLeaseWeightedAverageDiscountRatePercent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseWeightedAverageDiscountRatePercent" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseLiabilityCurrent" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseLiabilityCurrent" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeasePayments" xlink:label="OperatingLeasePayments" xlink:title="OperatingLeasePayments" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeasePayments" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeasePayments" order="15.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:label="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="OperatingLeaseLiabilitiesPaymentsDueAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseLiabilitiesPaymentsDueAbstract" order="16.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseExpense" xlink:label="OperatingLeaseExpense" xlink:title="OperatingLeaseExpense" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="OperatingLeaseExpense" xlink:title="definition: LesseeLeaseDescriptionLineItems to OperatingLeaseExpense" order="17.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" order="18.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" order="19.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDueYearThree" order="20.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDueYearFour" order="21.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDueYearFive" order="22.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" order="23.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="24.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" order="25.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="26.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="LesseeLeaseDescriptionTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="definition: LesseeLeaseDescriptionTable to ConsolidatedEntitiesAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain_2" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain_2" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:label="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:title="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:title="definition: PropertyPlantAndEquipmentTypeDomain to OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:label="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:title="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:title="definition: PropertyPlantAndEquipmentTypeDomain to OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeSpaceForCorporateHeadquartersMember" xlink:label="OfficeSpaceForCorporateHeadquartersMember" xlink:title="OfficeSpaceForCorporateHeadquartersMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="OfficeSpaceForCorporateHeadquartersMember" xlink:title="definition: PropertyPlantAndEquipmentTypeDomain to OfficeSpaceForCorporateHeadquartersMember" order="3.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/IncomeTaxesDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:label="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:title="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:label="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="UpfrontPaymentReceivedIncludingPurchaseOfStock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to UpfrontPaymentReceivedIncludingPurchaseOfStock" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfMilestonePaymentsAchieved" xlink:label="NumberOfMilestonePaymentsAchieved" xlink:title="NumberOfMilestonePaymentsAchieved" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NumberOfMilestonePaymentsAchieved" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NumberOfMilestonePaymentsAchieved" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MilestonePaymentsReceived" xlink:label="MilestonePaymentsReceived" xlink:title="MilestonePaymentsReceived" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="MilestonePaymentsReceived" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to MilestonePaymentsReceived" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfNewTargetsAdvanced" xlink:label="NumberOfNewTargetsAdvanced" xlink:title="NumberOfNewTargetsAdvanced" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NumberOfNewTargetsAdvanced" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NumberOfNewTargetsAdvanced" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:label="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="PaymentsIncludedInTransactionPriceForPerformanceObligation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to PaymentsIncludedInTransactionPriceForPerformanceObligation" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NextPotentialMilestonePayment" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NextPotentialMilestonePayment" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsBiogenMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.xsd#ions_ResearchAndDevelopmentServicesMember" xlink:label="ResearchAndDevelopmentServicesMember" xlink:title="ResearchAndDevelopmentServicesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentServicesMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentServicesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISMAPTMember" xlink:label="IONISMAPTMember" xlink:title="IONISMAPTMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="IONISMAPTMember" xlink:title="definition: ProductsAndServicesDomain to IONISMAPTMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISLRRK2Member" xlink:label="IONISLRRK2Member" xlink:title="IONISLRRK2Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="IONISLRRK2Member" xlink:title="definition: ProductsAndServicesDomain to IONISLRRK2Member" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_MilestonePaymentEarned" xlink:label="MilestonePaymentEarned" xlink:title="MilestonePaymentEarned" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="MilestonePaymentEarned" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to MilestonePaymentEarned" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NextPotentialMilestonePayment" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NextPotentialMilestonePayment" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="SubsequentEventTypeAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to SubsequentEventTypeAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="SubsequentEventTypeAxis" xlink:to="SubsequentEventTypeDomain" xlink:title="definition: SubsequentEventTypeAxis to SubsequentEventTypeDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain_2" xlink:title="SubsequentEventTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="SubsequentEventTypeAxis" xlink:to="SubsequentEventTypeDomain_2" xlink:title="definition: SubsequentEventTypeAxis to SubsequentEventTypeDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="SubsequentEventMember" xlink:title="SubsequentEventMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="SubsequentEventTypeDomain" xlink:to="SubsequentEventMember" xlink:title="definition: SubsequentEventTypeDomain to SubsequentEventMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_NumberOfDrugsCurrentlyBeingAdvanced" xlink:label="NumberOfDrugsCurrentlyBeingAdvanced" xlink:title="NumberOfDrugsCurrentlyBeingAdvanced" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NumberOfDrugsCurrentlyBeingAdvanced" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NumberOfDrugsCurrentlyBeingAdvanced" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NextPotentialMilestonePayment" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NextPotentialMilestonePayment" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LicenseMember" xlink:label="LicenseMember" xlink:title="LicenseMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="LicenseMember" xlink:title="definition: ProductsAndServicesDomain to LicenseMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_NumberOfCollaborationAgreements" xlink:label="NumberOfCollaborationAgreements" xlink:title="NumberOfCollaborationAgreements" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NumberOfCollaborationAgreements" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NumberOfCollaborationAgreements" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NextPotentialMilestonePayment" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NextPotentialMilestonePayment" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsRocheMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsRocheMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="definition: CollaborativeArrangementsAndLicensingAgreementsRocheMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.xsd#ions_IonisHttMember" xlink:label="IonisHttMember" xlink:title="IonisHttMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="IonisHttMember" xlink:title="definition: ProductsAndServicesDomain to IonisHttMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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="ions-20190930.xsd#ions_SublicenseFeePaidForLicenseOfDrug" xlink:label="SublicenseFeePaidForLicenseOfDrug" xlink:title="SublicenseFeePaidForLicenseOfDrug" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="SublicenseFeePaidForLicenseOfDrug" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to SublicenseFeePaidForLicenseOfDrug" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to ReceiptOfSharesInSubsidiary" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConsolidatedEntitiesAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain_2" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain_2" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.xsd#ions_AKCEAAPOALMember" xlink:label="AKCEAAPOALMember" xlink:title="AKCEAAPOALMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="AKCEAAPOALMember" xlink:title="definition: ProductsAndServicesDomain to AKCEAAPOALMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_UpfrontLicenseFeeToBeReceived" xlink:label="UpfrontLicenseFeeToBeReceived" xlink:title="UpfrontLicenseFeeToBeReceived" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="UpfrontLicenseFeeToBeReceived" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to UpfrontLicenseFeeToBeReceived" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfDrug" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to RoyaltyPercentageReceivedOnNetSalesOfDrug" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_SublicenseFeePaidForLicenseOfDrug" xlink:label="SublicenseFeePaidForLicenseOfDrug" xlink:title="SublicenseFeePaidForLicenseOfDrug" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="SublicenseFeePaidForLicenseOfDrug" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to SublicenseFeePaidForLicenseOfDrug" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to ReceiptOfSharesInSubsidiary" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConsolidatedEntitiesAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain_2" xlink:title="ConsolidatedEntitiesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain_2" xlink:title="definition: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="SubsequentEventTypeAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to SubsequentEventTypeAxis" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="SubsequentEventTypeAxis" xlink:to="SubsequentEventTypeDomain" xlink:title="definition: SubsequentEventTypeAxis to SubsequentEventTypeDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain_2" xlink:title="SubsequentEventTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="SubsequentEventTypeAxis" xlink:to="SubsequentEventTypeDomain_2" xlink:title="definition: SubsequentEventTypeAxis to SubsequentEventTypeDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="SubsequentEventMember" xlink:title="SubsequentEventMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="SubsequentEventTypeDomain" xlink:to="SubsequentEventMember" xlink:title="definition: SubsequentEventTypeDomain to SubsequentEventMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="StatementScenarioAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to StatementScenarioAxis" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain" xlink:title="definition: StatementScenarioAxis to ScenarioUnspecifiedDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain_2" xlink:title="ScenarioUnspecifiedDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain_2" xlink:title="definition: StatementScenarioAxis to ScenarioUnspecifiedDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScenarioUnspecifiedDomain" xlink:to="ScenarioForecastMember" xlink:title="definition: ScenarioUnspecifiedDomain to ScenarioForecastMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://isispharm.com/role/SegmentInformationDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingInformationLineItems" xlink:label="SegmentReportingInformationLineItems" xlink:title="SegmentReportingInformationLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="SegmentReportingInformationLineItems" xlink:to="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="definition: SegmentReportingInformationLineItems to SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingInformationLineItems" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="definition: SegmentReportingInformationLineItems to RevenueFromContractWithCustomerExcludingAssessedTax" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingInformationLineItems" xlink:to="CostsAndExpenses" xlink:title="definition: SegmentReportingInformationLineItems to CostsAndExpenses" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingInformationLineItems" xlink:to="OperatingIncomeLoss" xlink:title="definition: SegmentReportingInformationLineItems to OperatingIncomeLoss" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingInformationLineItems" xlink:to="Assets" xlink:title="definition: SegmentReportingInformationLineItems to Assets" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:label="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:title="ScheduleOfSegmentReportingInformationBySegmentTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="SegmentReportingInformationLineItems" xlink:to="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:title="definition: SegmentReportingInformationLineItems to ScheduleOfSegmentReportingInformationBySegmentTable" order="6.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsAxis" xlink:label="ConsolidationItemsAxis" xlink:title="ConsolidationItemsAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="ConsolidationItemsAxis" xlink:title="definition: ScheduleOfSegmentReportingInformationBySegmentTable to ConsolidationItemsAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsDomain" xlink:label="ConsolidationItemsDomain" xlink:title="ConsolidationItemsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConsolidationItemsAxis" xlink:to="ConsolidationItemsDomain" xlink:title="definition: ConsolidationItemsAxis to ConsolidationItemsDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsDomain" xlink:label="ConsolidationItemsDomain_2" xlink:title="ConsolidationItemsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConsolidationItemsAxis" xlink:to="ConsolidationItemsDomain_2" xlink:title="definition: ConsolidationItemsAxis to ConsolidationItemsDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingSegmentsMember" xlink:label="OperatingSegmentsMember" xlink:title="OperatingSegmentsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidationItemsDomain" xlink:to="OperatingSegmentsMember" xlink:title="definition: ConsolidationItemsDomain to OperatingSegmentsMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IntersegmentEliminationMember" xlink:label="IntersegmentEliminationMember" xlink:title="IntersegmentEliminationMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConsolidationItemsDomain" xlink:to="IntersegmentEliminationMember" xlink:title="definition: ConsolidationItemsDomain to IntersegmentEliminationMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="StatementBusinessSegmentsAxis" xlink:title="definition: ScheduleOfSegmentReportingInformationBySegmentTable to StatementBusinessSegmentsAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain" xlink:title="SegmentDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementBusinessSegmentsAxis" xlink:to="SegmentDomain" xlink:title="definition: StatementBusinessSegmentsAxis to SegmentDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain_2" xlink:title="SegmentDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementBusinessSegmentsAxis" xlink:to="SegmentDomain_2" xlink:title="definition: StatementBusinessSegmentsAxis to SegmentDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="SegmentDomain" xlink:to="IonisCoreMember" xlink:title="definition: SegmentDomain to IonisCoreMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsMember" xlink:label="AkceaTherapeuticsMember" xlink:title="AkceaTherapeuticsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="SegmentDomain" xlink:to="AkceaTherapeuticsMember" xlink:title="definition: SegmentDomain to AkceaTherapeuticsMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="ProductOrServiceAxis" xlink:title="definition: ScheduleOfSegmentReportingInformationBySegmentTable to ProductOrServiceAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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-20190930.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-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:title="definition: MinorityInterestLineItems to SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="MinorityInterestLineItems" xlink:to="MinorityInterestOwnershipPercentageByParent" xlink:title="definition: MinorityInterestLineItems to MinorityInterestOwnershipPercentageByParent" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="MinorityInterestLineItems" xlink:to="MinorityInterestTable" xlink:title="definition: MinorityInterestLineItems to MinorityInterestTable" order="3.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="MinorityInterestTable" xlink:to="OwnershipAxis" xlink:title="definition: MinorityInterestTable to OwnershipAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="definition: OwnershipAxis to OwnershipDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain_2" xlink:title="OwnershipDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="OwnershipAxis" xlink:to="OwnershipDomain_2" xlink:title="definition: OwnershipAxis to OwnershipDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="definition: OwnershipDomain to AkceaTherapeuticsIncMember" order="1.0" />
  </link:definitionLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>11
<FILENAME>ions-20190930_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 6.2.0.0 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.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract_lbl" xml:lang="en-US" id="dei_CoverAbstract_lbl">Cover [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CoverAbstract" xlink:to="dei_CoverAbstract_lbl" xlink:title="label: CoverAbstract to dei_CoverAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1_lbl" xml:lang="en-US" id="dei_EntityAddressAddressLine1_lbl">Entity Address, Address Line One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressAddressLine1" xlink:to="dei_EntityAddressAddressLine1_lbl" xlink:title="label: EntityAddressAddressLine1 to dei_EntityAddressAddressLine1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag_lbl" xml:lang="en-US" id="dei_AmendmentFlag_lbl">Amendment Flag</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmendmentFlag" xlink:to="dei_AmendmentFlag_lbl" xlink:title="label: AmendmentFlag to dei_AmendmentFlag_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode_lbl" xml:lang="en-US" id="dei_CityAreaCode_lbl">City Area Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CityAreaCode" xlink:to="dei_CityAreaCode_lbl" xlink:title="label: CityAreaCode to dei_CityAreaCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCityOrTown_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCityOrTown_lbl" xml:lang="en-US" id="dei_EntityAddressCityOrTown_lbl">Entity Address, City or Town</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressCityOrTown" xlink:to="dei_EntityAddressCityOrTown_lbl" xlink:title="label: EntityAddressCityOrTown to dei_EntityAddressCityOrTown_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_CurrentFiscalYearEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CurrentFiscalYearEndDate_lbl" xml:lang="en-US" id="dei_CurrentFiscalYearEndDate_lbl">Current Fiscal Year End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFiscalYearEndDate" xlink:to="dei_CurrentFiscalYearEndDate_lbl" xlink:title="label: CurrentFiscalYearEndDate to dei_CurrentFiscalYearEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate_lbl" xml:lang="en-US" id="dei_DocumentPeriodEndDate_lbl">Document Period End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate_lbl" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityIncorporationStateCountryCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityIncorporationStateCountryCode_lbl" xml:lang="en-US" id="dei_EntityIncorporationStateCountryCode_lbl">Entity Incorporation, State or Country Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityIncorporationStateCountryCode" xlink:to="dei_EntityIncorporationStateCountryCode_lbl" xlink:title="label: EntityIncorporationStateCountryCode to dei_EntityIncorporationStateCountryCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link:label xlink:type="resource" xlink:label="dei_LocalPhoneNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_LocalPhoneNumber_lbl" xml:lang="en-US" id="dei_LocalPhoneNumber_lbl">Local Phone Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LocalPhoneNumber" xlink:to="dei_LocalPhoneNumber_lbl" xlink:title="label: LocalPhoneNumber to dei_LocalPhoneNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressPostalZipCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressPostalZipCode_lbl" xml:lang="en-US" id="dei_EntityAddressPostalZipCode_lbl">Entity Address, Postal Zip Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressPostalZipCode" xlink:to="dei_EntityAddressPostalZipCode_lbl" xlink:title="label: EntityAddressPostalZipCode to dei_EntityAddressPostalZipCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressStateOrProvince_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressStateOrProvince_lbl" xml:lang="en-US" id="dei_EntityAddressStateOrProvince_lbl">Entity Address, State or Province</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressStateOrProvince" xlink:to="dei_EntityAddressStateOrProvince_lbl" xlink:title="label: EntityAddressStateOrProvince to dei_EntityAddressStateOrProvince_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link:label xlink:type="resource" xlink:label="dei_Security12bTitle_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_Security12bTitle_lbl" xml:lang="en-US" id="dei_Security12bTitle_lbl">Title of 12(b) Security</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Security12bTitle" xlink:to="dei_Security12bTitle_lbl" xlink:title="label: Security12bTitle to dei_Security12bTitle_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:label xlink:type="resource" xlink:label="dei_TradingSymbol_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_TradingSymbol_lbl" xml:lang="en-US" id="dei_TradingSymbol_lbl">Trading Symbol</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradingSymbol" xlink:to="dei_TradingSymbol_lbl" xlink:title="label: TradingSymbol to dei_TradingSymbol_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link:label xlink:type="resource" xlink:label="dei_SecurityExchangeName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_SecurityExchangeName_lbl" xml:lang="en-US" id="dei_SecurityExchangeName_lbl">Security Exchange Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecurityExchangeName" xlink:to="dei_SecurityExchangeName_lbl" xlink:title="label: SecurityExchangeName to dei_SecurityExchangeName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCurrentReportingStatus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCurrentReportingStatus_lbl" xml:lang="en-US" id="dei_EntityCurrentReportingStatus_lbl">Entity Current Reporting Status</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCurrentReportingStatus" xlink:to="dei_EntityCurrentReportingStatus_lbl" xlink:title="label: EntityCurrentReportingStatus to dei_EntityCurrentReportingStatus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFilerCategory_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFilerCategory_lbl" xml:lang="en-US" id="dei_EntityFilerCategory_lbl">Entity Filer Category</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFilerCategory" xlink:to="dei_EntityFilerCategory_lbl" xlink:title="label: EntityFilerCategory to dei_EntityFilerCategory_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName_lbl" xml:lang="en-US" id="dei_EntityRegistrantName_lbl">Entity Registrant Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityRegistrantName" xlink:to="dei_EntityRegistrantName_lbl" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey_lbl" xml:lang="en-US" id="dei_EntityCentralIndexKey_lbl">Entity Central Index Key</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey_lbl" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber_lbl" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber_lbl">Entity Tax Identification Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber_lbl" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCommonStockSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCommonStockSharesOutstanding_lbl" xml:lang="en-US" id="dei_EntityCommonStockSharesOutstanding_lbl">Entity Common Stock, Shares Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCommonStockSharesOutstanding" xlink:to="dei_EntityCommonStockSharesOutstanding_lbl" xlink:title="label: EntityCommonStockSharesOutstanding to dei_EntityCommonStockSharesOutstanding_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalYearFocus_lbl">Document Fiscal Year Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalYearFocus" xlink:to="dei_DocumentFiscalYearFocus_lbl" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus_lbl">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus_lbl" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType_lbl" xml:lang="en-US" id="dei_DocumentType_lbl">Document Type</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentType" xlink:to="dei_DocumentType_lbl" xlink:title="label: DocumentType to dei_DocumentType_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_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/2019/dei-2019-01-31.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentTransitionReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentTransitionReport_lbl" xml:lang="en-US" id="dei_DocumentTransitionReport_lbl">Document Transition Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentTransitionReport" xlink:to="dei_DocumentTransitionReport_lbl" xlink:title="label: DocumentTransitionReport to dei_DocumentTransitionReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:label xlink:type="resource" xlink:label="dei_EntityInteractiveDataCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityInteractiveDataCurrent_lbl" xml:lang="en-US" id="dei_EntityInteractiveDataCurrent_lbl">Entity Interactive Data Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityInteractiveDataCurrent" xlink:to="dei_EntityInteractiveDataCurrent_lbl" xlink:title="label: EntityInteractiveDataCurrent to dei_EntityInteractiveDataCurrent_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber_lbl" xml:lang="en-US" id="dei_EntityFileNumber_lbl">Entity File Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFileNumber" xlink:to="dei_EntityFileNumber_lbl" xlink:title="label: EntityFileNumber to dei_EntityFileNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityShellCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityShellCompany_lbl" xml:lang="en-US" id="dei_EntityShellCompany_lbl">Entity Shell Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityShellCompany" xlink:to="dei_EntityShellCompany_lbl" xlink:title="label: EntityShellCompany to dei_EntityShellCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany_lbl" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany_lbl">Entity Emerging Growth Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityEmergingGrowthCompany" xlink:to="dei_EntityEmergingGrowthCompany_lbl" xlink:title="label: EntityEmergingGrowthCompany to dei_EntityEmergingGrowthCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness_lbl" xml:lang="en-US" id="dei_EntitySmallBusiness_lbl">Entity Small Business</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntitySmallBusiness" xlink:to="dei_EntitySmallBusiness_lbl" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:label="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:title="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl" xml:lang="en-US" id="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl">Number of investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:to="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl" xlink:title="label: AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1 to us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl1" xml:lang="en-US" id="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl1">Available-for-sale, Securities in Unrealized Loss Positions, Qualitative Disclosure, Number of Positions</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:to="us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl1" xlink:title="label: AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1 to us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201602Member" xlink:label="AccountingStandardsUpdate201602Member" xlink:title="AccountingStandardsUpdate201602Member" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountingStandardsUpdate201602Member_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccountingStandardsUpdate201602Member_lbl" xml:lang="en-US" id="us-gaap_AccountingStandardsUpdate201602Member_lbl">Topic 842 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountingStandardsUpdate201602Member" xlink:to="us-gaap_AccountingStandardsUpdate201602Member_lbl" xlink:title="label: AccountingStandardsUpdate201602Member to us-gaap_AccountingStandardsUpdate201602Member_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountingStandardsUpdate201602Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccountingStandardsUpdate201602Member_lbl1" xml:lang="en-US" id="us-gaap_AccountingStandardsUpdate201602Member_lbl1">Accounting Standards Update 2016-02 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountingStandardsUpdate201602Member" xlink:to="us-gaap_AccountingStandardsUpdate201602Member_lbl1" xlink:title="label: AccountingStandardsUpdate201602Member to us-gaap_AccountingStandardsUpdate201602Member_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/negatedLabel" xlink:title="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl" xml:lang="en-US" id="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl">Amortization of premium (discount) 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" xlink:title="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl">Adjustments to reconcile net loss to net cash provided by 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:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl1">Adjustments to Reconcile Net Income (Loss) to 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="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:title="label: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 share-based 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="AdjustmentsForNewAccountingPronouncementsAxis" xlink:title="AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_lbl">Adjustments for New Accounting Pronouncements [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_lbl" xlink:title="label: AdjustmentsForNewAccountingPronouncementsAxis to us-gaap_AdjustmentsForNewAccountingPronouncementsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfDebtDiscountPremium" xlink:label="AmortizationOfDebtDiscountPremium" xlink:title="AmortizationOfDebtDiscountPremium" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xml:lang="en-US" id="us-gaap_AmortizationOfDebtDiscountPremium_lbl">Amortization of convertible senior notes discount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfDebtDiscountPremium" xlink:to="us-gaap_AmortizationOfDebtDiscountPremium_lbl" xlink:title="label: AmortizationOfDebtDiscountPremium to us-gaap_AmortizationOfDebtDiscountPremium_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetImpairmentCharges" xlink:label="AssetImpairmentCharges" xlink:title="AssetImpairmentCharges" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetImpairmentCharges_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetImpairmentCharges_lbl" xml:lang="en-US" id="us-gaap_AssetImpairmentCharges_lbl">Non-cash losses related to patents, licensing and property, plant and equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetImpairmentCharges" xlink:to="us-gaap_AssetImpairmentCharges_lbl" xlink:title="label: AssetImpairmentCharges to us-gaap_AssetImpairmentCharges_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetImpairmentCharges_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetImpairmentCharges_lbl1" xml:lang="en-US" id="us-gaap_AssetImpairmentCharges_lbl1">Asset Impairment Charges</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetImpairmentCharges" xlink:to="us-gaap_AssetImpairmentCharges_lbl1" xlink:title="label: AssetImpairmentCharges to us-gaap_AssetImpairmentCharges_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Total assets as of current period</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl">Unrealized losses, total temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl1">Available-for-sale Securities, Continuous Unrealized Loss Position, Accumulated Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl">Unrealized losses, 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="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1">Available-for-sale Securities, 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="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl">Unrealized losses, 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="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1">Available-for-sale Securities, 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="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecurities" xlink:label="AvailableForSaleSecurities" xlink:title="AvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecurities_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_AvailableForSaleSecurities_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecurities_lbl">Available-for-sale securities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecurities" xlink:to="us-gaap_AvailableForSaleSecurities_lbl" xlink:title="label: AvailableForSaleSecurities to us-gaap_AvailableForSaleSecurities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecurities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecurities_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecurities_lbl1">Available-for-sale Securities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecurities" xlink:to="us-gaap_AvailableForSaleSecurities_lbl1" xlink:title="label: AvailableForSaleSecurities to us-gaap_AvailableForSaleSecurities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl">Estimated fair value, total temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl1">Available-for-sale Securities, Continuous Unrealized Loss Position, Fair Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl">Estimated fair value, 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="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl1">Available-for-sale Securities, Continuous Unrealized Loss Position, Twelve Months or Longer, Fair Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl">Estimated fair value, 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="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl1">Available-for-sale Securities, Continuous Unrealized Loss Position, Less than Twelve Months, Fair Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/label" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1">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_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtSecurities to us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CapitalExpendituresIncurredButNotYetPaid" xlink:label="CapitalExpendituresIncurredButNotYetPaid" xlink:title="CapitalExpendituresIncurredButNotYetPaid" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl" xml:lang="en-US" id="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl">Purchases of property, plant and equipment included in long-term obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CapitalExpendituresIncurredButNotYetPaid" xlink:to="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl" xlink:title="label: CapitalExpendituresIncurredButNotYetPaid to us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl1" xml:lang="en-US" id="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl1">Capital Expenditures Incurred but Not yet Paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CapitalExpendituresIncurredButNotYetPaid" xlink:to="us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl1" xlink:title="label: CapitalExpendituresIncurredButNotYetPaid to us-gaap_CapitalExpendituresIncurredButNotYetPaid_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl">Net 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="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl1" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl1">Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents, Period Increase (Decrease), Excluding Exchange Rate Effect</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl1" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashAndCashEquivalentsMember" xlink:label="CashAndCashEquivalentsMember" xlink:title="CashAndCashEquivalentsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsMember_lbl" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsMember_lbl">Cash and Cash Equivalents [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsMember" xlink:to="us-gaap_CashAndCashEquivalentsMember_lbl" xlink:title="label: CashAndCashEquivalentsMember to us-gaap_CashAndCashEquivalentsMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:label="ClassOfStockDomain" xlink:title="ClassOfStockDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ClassOfStockDomain_lbl" xml:lang="en-US" id="us-gaap_ClassOfStockDomain_lbl">Class of Stock [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClassOfStockDomain" xlink:to="us-gaap_ClassOfStockDomain_lbl" xlink:title="label: ClassOfStockDomain to us-gaap_ClassOfStockDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:label="CommonStockCapitalSharesReservedForFutureIssuance" xlink:title="CommonStockCapitalSharesReservedForFutureIssuance" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl" xml:lang="en-US" id="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl">Common shares reserved for future issuance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockCapitalSharesReservedForFutureIssuance" xlink:to="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl" xlink:title="label: CommonStockCapitalSharesReservedForFutureIssuance to us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1" xml:lang="en-US" id="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1">Common Stock, Capital Shares Reserved for Future Issuance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockCapitalSharesReservedForFutureIssuance" xlink:to="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1" xlink:title="label: CommonStockCapitalSharesReservedForFutureIssuance to us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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, 140,636,397 and 137,928,828 shares issued and outstanding at September 30, 2019 (unaudited) and December 31, 2018, 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:label="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:title="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl">Comprehensive loss attributable to noncontrolling interests</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:to="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl" xlink:title="label: ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest to us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl1">Comprehensive Income (Loss), Net of Tax, Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:to="us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl1" xlink:title="label: ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest to us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:label="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:title="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl">Comprehensive income (loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:title="label: ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest to us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl1">Comprehensive Income (Loss), Net of Tax, 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="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest to us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:label="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:title="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" xml:lang="en-US" id="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl">Noncontrolling Interest in Akcea Therapeutics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:to="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" xlink:title="label: ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy to us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1" xml:lang="en-US" id="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1">Consolidation, Subsidiaries or Other Investments, Consolidated Entities, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:to="us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1" xlink:title="label: ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy to us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl">Long-term deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1">Contract with Customer, Liability, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiability_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl">Deferred revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl1">Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl1" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl">Revenue recognized from amounts in beginning deferred revenue balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1">Contract with Customer, Liability, Revenue Recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl">Deferred Revenue [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1">Contract with Customer, Liability [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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, Net, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl">Current portion of deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Contract with Customer, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractReceivablesAbstract" xlink:label="ContractReceivablesAbstract" xlink:title="ContractReceivablesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractReceivablesAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractReceivablesAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl1">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl1" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConvertiblePreferredStockMember" xlink:label="ConvertiblePreferredStockMember" xlink:title="ConvertiblePreferredStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertiblePreferredStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertiblePreferredStockMember_lbl" xml:lang="en-US" id="us-gaap_ConvertiblePreferredStockMember_lbl">Preferred Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertiblePreferredStockMember" xlink:to="us-gaap_ConvertiblePreferredStockMember_lbl" xlink:title="label: ConvertiblePreferredStockMember to us-gaap_ConvertiblePreferredStockMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertiblePreferredStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertiblePreferredStockMember_lbl1" xml:lang="en-US" id="us-gaap_ConvertiblePreferredStockMember_lbl1">Convertible Preferred Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertiblePreferredStockMember" xlink:to="us-gaap_ConvertiblePreferredStockMember_lbl1" xlink:title="label: ConvertiblePreferredStockMember to us-gaap_ConvertiblePreferredStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">1 percent convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl1">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostOfGoodsAndServicesSoldAbstract" xlink:label="CostOfGoodsAndServicesSoldAbstract" xlink:title="CostOfGoodsAndServicesSoldAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl">Cost of Products Sold [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSoldAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" xlink:title="label: CostOfGoodsAndServicesSoldAbstract to us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1">Cost of Goods and Services Sold [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSoldAbstract" xlink:to="us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" xlink:title="label: CostOfGoodsAndServicesSoldAbstract to us-gaap_CostOfGoodsAndServicesSoldAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl">Cost of products sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl1">Cost of Goods and Services Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostOfSalesPolicyTextBlock" xlink:label="CostOfSalesPolicyTextBlock" xlink:title="CostOfSalesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl">Cost of Products Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl1">Cost of Goods and Service [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesMember_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl">Cost of Products Sold [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesMember_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl1">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl1" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpenses_lbl2" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl2">Costs and Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl2" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl">Expenses:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl">Strategic Partner [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl1" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl1">Customer Concentration Risk [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueLineItems_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueLineItems_lbl">Disaggregation of Revenue [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:title="label: DisaggregationOfRevenueLineItems to us-gaap_DisaggregationOfRevenueLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueTable_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTable_lbl">Disaggregation of Revenue [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DisaggregationOfRevenueTable" xlink:to="us-gaap_DisaggregationOfRevenueTable_lbl" xlink:title="label: DisaggregationOfRevenueTable to us-gaap_DisaggregationOfRevenueTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentAxis_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentAxis_lbl">Debt Instrument [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentAxis_lbl" xlink:title="label: DebtInstrumentAxis to us-gaap_DebtInstrumentAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentNameDomain_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentNameDomain_lbl">Debt Instrument, Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNameDomain" xlink:to="us-gaap_DebtInstrumentNameDomain_lbl" xlink:title="label: DebtInstrumentNameDomain to us-gaap_DebtInstrumentNameDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Debt Instrument, Interest Rate, Stated Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:label="DeferredIncomeTaxExpenseBenefit" xlink:title="DeferredIncomeTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl" xml:lang="en-US" id="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl">Provision for deferred income taxes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredIncomeTaxExpenseBenefit" xlink:to="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl" xlink:title="label: DeferredIncomeTaxExpenseBenefit to us-gaap_DeferredIncomeTaxExpenseBenefit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl1">Deferred Income Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredIncomeTaxExpenseBenefit" xlink:to="us-gaap_DeferredIncomeTaxExpenseBenefit_lbl1" xlink:title="label: DeferredIncomeTaxExpenseBenefit to us-gaap_DeferredIncomeTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:label="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:title="DeferredTaxAssetsLiabilitiesNetNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl" xml:lang="en-US" id="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl">Long-term deferred tax assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:to="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl" xlink:title="label: DeferredTaxAssetsLiabilitiesNetNoncurrent to us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl1">Deferred Tax Assets, Net, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:to="us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl1" xlink:title="label: DeferredTaxAssetsLiabilitiesNetNoncurrent to us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:label="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:title="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl" xml:lang="en-US" id="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_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="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:to="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl" xlink:title="label: DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract to us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl1">Share-based Payment Arrangement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:to="us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl1" xlink:title="label: DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract to us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" xlink:title="us-gaap_EarningsPerShareDiluted_lbl" xml:lang="en-US" id="us-gaap_EarningsPerShareDiluted_lbl">Diluted net income 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:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareDiluted_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareDiluted_lbl1" xml:lang="en-US" id="us-gaap_EarningsPerShareDiluted_lbl1">Diluted net income (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_lbl1" xlink:title="label: EarningsPerShareDiluted to us-gaap_EarningsPerShareDiluted_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 income (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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 Income (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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 Income (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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:label="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:title="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl">Federal statutory rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl" xlink:title="label: EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate to us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl1">Effective Income Tax Rate Reconciliation, at Federal Statutory Income Tax Rate, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl1" xlink:title="label: EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate to us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:label="EffectiveIncomeTaxRateContinuingOperations" xlink:title="EffectiveIncomeTaxRateContinuingOperations" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl">Effective tax rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl" xlink:title="label: EffectiveIncomeTaxRateContinuingOperations to us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl1">Effective Income Tax Rate Reconciliation, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateContinuingOperations" xlink:to="us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl1" xlink:title="label: EffectiveIncomeTaxRateContinuingOperations to us-gaap_EffectiveIncomeTaxRateContinuingOperations_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:label="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:title="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl">Income Taxes [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:to="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl" xlink:title="label: EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract to us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl1">Effective Income Tax Rate Reconciliation, Percent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:to="us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl1" xlink:title="label: EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract to us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 RSUs</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Employee Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EmployeeStockOptionMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl1">Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl1" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockOptionMember_lbl2" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl2">Share-based Payment Arrangement, Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl2" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 in ProQR Therapeutics N.V.</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</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1">Fair Value, Net Asset (Liability) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IntersegmentEliminationMember" xlink:label="IntersegmentEliminationMember" xlink:title="IntersegmentEliminationMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IntersegmentEliminationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IntersegmentEliminationMember_lbl" xml:lang="en-US" id="us-gaap_IntersegmentEliminationMember_lbl">Elimination of Intercompany Activity [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IntersegmentEliminationMember" xlink:to="us-gaap_IntersegmentEliminationMember_lbl" xlink:title="label: IntersegmentEliminationMember to us-gaap_IntersegmentEliminationMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) [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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl" xml:lang="en-US" id="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl">Income (loss) before income tax (expense) benefit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl" xlink:title="label: IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments to us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl1" xml:lang="en-US" id="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl1">Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl1" xlink:title="label: IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments to us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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) 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_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 (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_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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1">Increase (Decrease) in Other Employee-Related Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl" xml:lang="en-US" id="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl">Shares issuable related to stock-based compensation (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:to="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl" xlink:title="label: IncrementalCommonSharesAttributableToShareBasedPaymentArrangements to us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InterestPaidNet_lbl" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl">Interest paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPaidNet_lbl1" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl1">Interest Paid, Excluding Capitalized Interest, Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl1" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InventoryWriteDown" xlink:label="InventoryWriteDown" xlink:title="InventoryWriteDown" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWriteDown_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWriteDown_lbl" xml:lang="en-US" id="us-gaap_InventoryWriteDown_lbl">Inventory write-off</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWriteDown" xlink:to="us-gaap_InventoryWriteDown_lbl" xlink:title="label: InventoryWriteDown to us-gaap_InventoryWriteDown_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWriteDown_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWriteDown_lbl1" xml:lang="en-US" id="us-gaap_InventoryWriteDown_lbl1">Inventory Write-down</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWriteDown" xlink:to="us-gaap_InventoryWriteDown_lbl1" xlink:title="label: InventoryWriteDown to us-gaap_InventoryWriteDown_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:label="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:title="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl" xml:lang="en-US" id="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl">Inventory Valuation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:to="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl" xlink:title="label: InventoryRawMaterialsAndSuppliesNetOfReservesAbstract to us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl1" xml:lang="en-US" id="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl1">Inventory, Raw Materials and Supplies, Net of Reserves [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:to="us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl1" xlink:title="label: InventoryRawMaterialsAndSuppliesNetOfReservesAbstract to us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InventoryPolicyTextBlock" xlink:label="InventoryPolicyTextBlock" xlink:title="InventoryPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl">Inventory Valuation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl1">Inventory, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/label" xlink:title="us-gaap_InventoryNet_lbl1" xml:lang="en-US" id="us-gaap_InventoryNet_lbl1">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_lbl1" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember" xlink:title="InvestmentTypeCategorizationMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTypeCategorizationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTypeCategorizationMember_lbl" xml:lang="en-US" id="us-gaap_InvestmentTypeCategorizationMember_lbl">Investments [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTypeCategorizationMember" xlink:to="us-gaap_InvestmentTypeCategorizationMember_lbl" xlink:title="label: InvestmentTypeCategorizationMember to us-gaap_InvestmentTypeCategorizationMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsLineItems_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsLineItems_lbl">Investment Holdings [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsLineItems" xlink:to="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:title="label: InvestmentHoldingsLineItems to us-gaap_InvestmentHoldingsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentIncomeNet_lbl" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl">Investment income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl1" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl1">Investment Income, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl1" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="InvestmentTypeAxis" xlink:title="InvestmentTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTypeAxis_lbl" xml:lang="en-US" id="us-gaap_InvestmentTypeAxis_lbl">Investment Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTypeAxis" xlink:to="us-gaap_InvestmentTypeAxis_lbl" xlink:title="label: InvestmentTypeAxis to us-gaap_InvestmentTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeasesTextBlock" xlink:label="LesseeOperatingLeasesTextBlock" xlink:title="LesseeOperatingLeasesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl">Operating Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasesTextBlock" xlink:to="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xlink:title="label: LesseeOperatingLeasesTextBlock to us-gaap_LesseeOperatingLeasesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl1">Lessee, Operating Leases [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasesTextBlock" xlink:to="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xlink:title="label: LesseeOperatingLeasesTextBlock to us-gaap_LesseeOperatingLeasesTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Operating Leased Assets [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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl">Thereafter</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1">Lessee, Operating Lease, Liability, Payments, Due after Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl">Remainder of 2019</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1">Lessee, Operating Lease, Liability, Payments, Due Next Twelve Months</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl">2022</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFour to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1">Lessee, Operating Lease, Liability, Payments, Due Year Four</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFour to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl">2023</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1">Lessee, Operating Lease, Liability, Payments, Due Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/totalLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl">Total minimum lease payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_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, Payments, Due</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="LesseeOperatingLeaseRenewalTerm" xlink:title="LesseeOperatingLeaseRenewalTerm" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl">Term of lease extension</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1">Lessee, Operating Lease, Renewal Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Schedule of Operating Leased Assets [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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl">Imputed interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityUndiscountedExcessAmount to us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1">Lessee, Operating Lease, Liability, Undiscounted Excess Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityUndiscountedExcessAmount to us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl">Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl1">Lessee, Leases [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl">2021</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearThree to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1">Lessee, Operating Lease, Liability, Payments, Due Year Three</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearThree to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl">2020</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearTwo to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1">Lessee, Operating Lease, Liability, Payments, Due Year Two</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearTwo to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract_lbl">Term of lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseTermOfContract" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xlink:title="label: LesseeOperatingLeaseTermOfContract to us-gaap_LesseeOperatingLeaseTermOfContract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1">Lessee, Operating Lease, Term of Contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseTermOfContract" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xlink:title="label: LesseeOperatingLeaseTermOfContract to us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl">Operating Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl1">Lessee Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeasesAbstract" xlink:label="LeasesAbstract" xlink:title="LeasesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeasesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LeasesAbstract_lbl" xml:lang="en-US" id="us-gaap_LeasesAbstract_lbl">Operating Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeasesAbstract" xlink:to="us-gaap_LeasesAbstract_lbl" xlink:title="label: LeasesAbstract to us-gaap_LeasesAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl">Current liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl1">Liabilities, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl">Total current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl1">Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl1" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LicenseMember" xlink:label="LicenseMember" xlink:title="LicenseMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LicenseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LicenseMember_lbl" xml:lang="en-US" id="us-gaap_LicenseMember_lbl">License Fees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseMember" xlink:to="us-gaap_LicenseMember_lbl" xlink:title="label: LicenseMember to us-gaap_LicenseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LicenseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LicenseMember_lbl1" xml:lang="en-US" id="us-gaap_LicenseMember_lbl1">License [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicenseMember" xlink:to="us-gaap_LicenseMember_lbl1" xlink:title="label: LicenseMember to us-gaap_LicenseMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:label="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="LongTermDebtAndCapitalLeaseObligationsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl">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="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" xlink:title="label: LongTermDebtAndCapitalLeaseObligationsCurrent to us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1">Long-term Debt and Lease Obligation, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:to="us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" xlink:title="label: LongTermDebtAndCapitalLeaseObligationsCurrent to us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermLoansFromBank_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermLoansFromBank_lbl" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl">Long-term mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermLoansFromBank" xlink:to="us-gaap_LongTermLoansFromBank_lbl" xlink:title="label: LongTermLoansFromBank to us-gaap_LongTermLoansFromBank_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestPeriodIncreaseDecrease" xlink:label="MinorityInterestPeriodIncreaseDecrease" xlink:title="MinorityInterestPeriodIncreaseDecrease" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl">Noncontrolling interest in Akcea Therapetuics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestPeriodIncreaseDecrease" xlink:to="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xlink:title="label: MinorityInterestPeriodIncreaseDecrease to us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1">Noncontrolling Interest, Period Increase (Decrease)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestPeriodIncreaseDecrease" xlink:to="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xlink:title="label: MinorityInterestPeriodIncreaseDecrease to us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterest" xlink:label="MinorityInterest" xlink:title="MinorityInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterest_lbl" xml:lang="en-US" id="us-gaap_MinorityInterest_lbl">Noncontrolling interest in Akcea Therapeutics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterest" xlink:to="us-gaap_MinorityInterest_lbl" xlink:title="label: MinorityInterest to us-gaap_MinorityInterest_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestLineItems_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestLineItems_lbl">Noncontrolling Interest [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestLineItems" xlink:to="us-gaap_MinorityInterestLineItems_lbl" xlink:title="label: MinorityInterestLineItems to us-gaap_MinorityInterestLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl">Percentage ownership</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestOwnershipPercentageByParent" xlink:to="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" xlink:title="label: MinorityInterestOwnershipPercentageByParent to us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1">Noncontrolling Interest, Ownership Percentage by Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestOwnershipPercentageByParent" xlink:to="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" xlink:title="label: MinorityInterestOwnershipPercentageByParent to us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestTable_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestTable_lbl">Noncontrolling Interest [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestTable" xlink:to="us-gaap_MinorityInterestTable_lbl" xlink:title="label: MinorityInterestTable to us-gaap_MinorityInterestTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 provided by operating activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1">Net Cash Provided by (Used in) Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl">Investing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Investing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 provided by 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetIncomeLoss_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl1">Net income (loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl1" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_NetIncomeLoss_lbl2" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl2">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl2" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl2" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLoss_lbl3" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl3">Net Income (Loss) Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl3" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl3" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic" xlink:label="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:title="NetIncomeLossAvailableToCommonStockholdersBasic" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl">Net income (loss) available to Ionis common shareholders</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:to="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl" xlink:title="label: NetIncomeLossAvailableToCommonStockholdersBasic to us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:label="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:title="NetIncomeLossAvailableToCommonStockholdersDiluted" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl">Income available to Ionis common shareholders</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:to="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl" xlink:title="label: NetIncomeLossAvailableToCommonStockholdersDiluted to us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl1" xml:lang="en-US" id="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl1">Net Income (Loss) Available to Common Stockholders, Diluted</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:to="us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl1" xlink:title="label: NetIncomeLossAvailableToCommonStockholdersDiluted to us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAttributableToNoncontrollingInterest" xlink:label="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="NetIncomeLossAttributableToNoncontrollingInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl">Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLossAttributableToNoncontrollingInterest" xlink:to="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl" xlink:title="label: NetIncomeLossAttributableToNoncontrollingInterest to us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl1">Net Income (Loss) Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLossAttributableToNoncontrollingInterest" xlink:to="us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl1" xlink:title="label: NetIncomeLossAttributableToNoncontrollingInterest to us-gaap_NetIncomeLossAttributableToNoncontrollingInterest_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:label="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:title="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_lbl" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_lbl">New Accounting Pronouncements or Change in Accounting Principle [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_lbl" xlink:title="label: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems to us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:label="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:title="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_lbl" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_lbl">New Accounting Pronouncements or Change in Accounting Principle [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_lbl" xlink:title="label: NewAccountingPronouncementsOrChangeInAccountingPrincipleTable to us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NumberOfReportableSegments" xlink:label="NumberOfReportableSegments" xlink:title="NumberOfReportableSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfReportableSegments_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NumberOfReportableSegments_lbl" xml:lang="en-US" id="us-gaap_NumberOfReportableSegments_lbl">Number of reportable segments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfReportableSegments" xlink:to="us-gaap_NumberOfReportableSegments_lbl" xlink:title="label: NumberOfReportableSegments to us-gaap_NumberOfReportableSegments_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NoncontrollingInterestAbstract" xlink:label="NoncontrollingInterestAbstract" xlink:title="NoncontrollingInterestAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NoncontrollingInterestAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_NoncontrollingInterestAbstract_lbl" xml:lang="en-US" id="us-gaap_NoncontrollingInterestAbstract_lbl">Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoncontrollingInterestAbstract" xlink:to="us-gaap_NoncontrollingInterestAbstract_lbl" xlink:title="label: NoncontrollingInterestAbstract to us-gaap_NoncontrollingInterestAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NoncontrollingInterestAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NoncontrollingInterestAbstract_lbl1" xml:lang="en-US" id="us-gaap_NoncontrollingInterestAbstract_lbl1">Noncontrolling Interest [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoncontrollingInterestAbstract" xlink:to="us-gaap_NoncontrollingInterestAbstract_lbl1" xlink:title="label: NoncontrollingInterestAbstract to us-gaap_NoncontrollingInterestAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NoncontrollingInterestMember" xlink:label="NoncontrollingInterestMember" xlink:title="NoncontrollingInterestMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NoncontrollingInterestMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NoncontrollingInterestMember_lbl" xml:lang="en-US" id="us-gaap_NoncontrollingInterestMember_lbl">Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoncontrollingInterestMember" xlink:to="us-gaap_NoncontrollingInterestMember_lbl" xlink:title="label: NoncontrollingInterestMember to us-gaap_NoncontrollingInterestMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:label="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="OperatingLeaseLiabilitiesPaymentsDueAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl">Annual Future Minimum Payments Under Operating Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" xlink:title="label: OperatingLeaseLiabilitiesPaymentsDueAbstract to us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1">Lessee, Operating Lease, Liability, Payment, Due [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xlink:title="label: OperatingLeaseLiabilitiesPaymentsDueAbstract to us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:label="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="OperatingLeaseWeightedAverageRemainingLeaseTerm1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl">Weighted average remaining lease term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:to="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl" xlink:title="label: OperatingLeaseWeightedAverageRemainingLeaseTerm1 to us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1">Operating Lease, Weighted Average Remaining Lease Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:to="us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" xlink:title="label: OperatingLeaseWeightedAverageRemainingLeaseTerm1 to us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset_lbl">Right-of-use operating lease assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAsset" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xlink:title="label: OperatingLeaseRightOfUseAsset to us-gaap_OperatingLeaseRightOfUseAsset_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset_lbl1">Operating Lease, Right-of-Use Asset</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAsset" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xlink:title="label: OperatingLeaseRightOfUseAsset to us-gaap_OperatingLeaseRightOfUseAsset_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseExpense" xlink:label="OperatingLeaseExpense" xlink:title="OperatingLeaseExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseExpense_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseExpense_lbl">Rent expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseExpense" xlink:to="us-gaap_OperatingLeaseExpense_lbl" xlink:title="label: OperatingLeaseExpense to us-gaap_OperatingLeaseExpense_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingSegmentsMember" xlink:label="OperatingSegmentsMember" xlink:title="OperatingSegmentsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingSegmentsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingSegmentsMember_lbl" xml:lang="en-US" id="us-gaap_OperatingSegmentsMember_lbl">Operating Segments [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingSegmentsMember" xlink:to="us-gaap_OperatingSegmentsMember_lbl" xlink:title="label: OperatingSegmentsMember to us-gaap_OperatingSegmentsMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent" xlink:label="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="OperatingLeaseWeightedAverageDiscountRatePercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl">Weighted average discount rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:to="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" xlink:title="label: OperatingLeaseWeightedAverageDiscountRatePercent to us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1">Operating Lease, Weighted Average Discount Rate, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:to="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xlink:title="label: OperatingLeaseWeightedAverageDiscountRatePercent to us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Income (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/verboseLabel" xlink:title="us-gaap_OperatingIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl1">Income (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_lbl1" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingIncomeLoss_lbl2" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl2">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_lbl2" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent_lbl">Current portion of operating lease liabilties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xlink:title="label: OperatingLeaseLiabilityCurrent to us-gaap_OperatingLeaseLiabilityCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent_lbl1">Operating Lease, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xlink:title="label: OperatingLeaseLiabilityCurrent to us-gaap_OperatingLeaseLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeasePayments" xlink:label="OperatingLeasePayments" xlink:title="OperatingLeasePayments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeasePayments_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeasePayments_lbl" xml:lang="en-US" id="us-gaap_OperatingLeasePayments_lbl">Operating lease cash payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeasePayments" xlink:to="us-gaap_OperatingLeasePayments_lbl" xlink:title="label: OperatingLeasePayments to us-gaap_OperatingLeasePayments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeasePayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeasePayments_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeasePayments_lbl1">Operating Lease, Payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeasePayments" xlink:to="us-gaap_OperatingLeasePayments_lbl1" xlink:title="label: OperatingLeasePayments to us-gaap_OperatingLeasePayments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiability_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl">Total operating lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_OperatingLeaseLiability_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl1">Operating lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl1" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiability_lbl2" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl2">Operating Lease, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl2" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/label" xlink:title="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl">Unrealized gains (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:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 (expenses)</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" xlink:title="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl">Change in unrealized gains (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:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl1" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl1">Other Comprehensive Income (Loss), Available-for-sale Securities Adjustment, Net of Tax, Portion Attributable to Parent</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_lbl1" xlink:title="label: OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent to us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ParentMember" xlink:label="ParentMember" xlink:title="ParentMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ParentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ParentMember_lbl" xml:lang="en-US" id="us-gaap_ParentMember_lbl">Total Ionis Stockholders' Equity [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ParentMember" xlink:to="us-gaap_ParentMember_lbl" xlink:title="label: ParentMember to us-gaap_ParentMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="PlanNameAxis" xlink:title="PlanNameAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PlanNameAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PlanNameAxis_lbl" xml:lang="en-US" id="us-gaap_PlanNameAxis_lbl">Plan Name [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PlanNameAxis" xlink:to="us-gaap_PlanNameAxis_lbl" xlink:title="label: PlanNameAxis to us-gaap_PlanNameAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="PlanNameDomain" xlink:title="PlanNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PlanNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PlanNameDomain_lbl" xml:lang="en-US" id="us-gaap_PlanNameDomain_lbl">Plan Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PlanNameDomain" xlink:to="us-gaap_PlanNameDomain_lbl" xlink:title="label: PlanNameDomain to us-gaap_PlanNameDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="ProceedsFromIssuanceOfCommonStock" xlink:title="ProceedsFromIssuanceOfCommonStock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl">Proceeds from the issuance of common stock to Biogen</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfCommonStock" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl" xlink:title="label: ProceedsFromIssuanceOfCommonStock to us-gaap_ProceedsFromIssuanceOfCommonStock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl1">Proceeds from Issuance of Common Stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfCommonStock" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock_lbl1" xlink:title="label: ProceedsFromIssuanceOfCommonStock to us-gaap_ProceedsFromIssuanceOfCommonStock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:label="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:title="ProceedsFromIssuanceOrSaleOfEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl">Basis of Presentation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:to="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl" xlink:title="label: ProceedsFromIssuanceOrSaleOfEquityAbstract to us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl1">Proceeds from Issuance or Sale of Equity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:to="us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl1" xlink:title="label: ProceedsFromIssuanceOrSaleOfEquityAbstract to us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 awards</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Product Sales, 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProfitLoss_lbl" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl">Net income (loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ProfitLoss_lbl1" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl1">Net income (loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl1" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProfitLoss_lbl2" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl2">Net Income (Loss), Including Portion Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl2" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Property, Plant and Equipment, Type [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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Property, Plant and Equipment, Type [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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:label="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl" xml:lang="en-US" id="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl">Right-of-use assets obtained in exchange for lease obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:to="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl" xlink:title="label: RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability to us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl1" xml:lang="en-US" id="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl1">Right-of-Use Asset Obtained in Exchange for Operating Lease Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:to="us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl1" xlink:title="label: RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability to us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="RelatedPartyTransactionsByRelatedPartyAxis" xlink:title="RelatedPartyTransactionsByRelatedPartyAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_lbl" xml:lang="en-US" id="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_lbl">Related Party [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_lbl" xlink:title="label: RelatedPartyTransactionsByRelatedPartyAxis to us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:label="RelatedPartyDomain" xlink:title="RelatedPartyDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RelatedPartyDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RelatedPartyDomain_lbl" xml:lang="en-US" id="us-gaap_RelatedPartyDomain_lbl">Related Party [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RelatedPartyDomain" xlink:to="us-gaap_RelatedPartyDomain_lbl" xlink:title="label: RelatedPartyDomain to us-gaap_RelatedPartyDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:label="RepaymentsOfLongTermDebt" xlink:title="RepaymentsOfLongTermDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RepaymentsOfLongTermDebt_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_RepaymentsOfLongTermDebt_lbl" xml:lang="en-US" id="us-gaap_RepaymentsOfLongTermDebt_lbl">Principal payments on debt obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RepaymentsOfLongTermDebt" xlink:to="us-gaap_RepaymentsOfLongTermDebt_lbl" xlink:title="label: RepaymentsOfLongTermDebt to us-gaap_RepaymentsOfLongTermDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RepaymentsOfLongTermDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RepaymentsOfLongTermDebt_lbl1" xml:lang="en-US" id="us-gaap_RepaymentsOfLongTermDebt_lbl1">Repayments of Long-term Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RepaymentsOfLongTermDebt" xlink:to="us-gaap_RepaymentsOfLongTermDebt_lbl1" xlink:title="label: RepaymentsOfLongTermDebt to us-gaap_RepaymentsOfLongTermDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="RestrictedStockMember" xlink:title="RestrictedStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestrictedStockMember_lbl" xml:lang="en-US" id="us-gaap_RestrictedStockMember_lbl">Restricted Stock Awards [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockMember" xlink:to="us-gaap_RestrictedStockMember_lbl" xlink:title="label: RestrictedStockMember to us-gaap_RestrictedStockMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestrictedStockMember_lbl1" xml:lang="en-US" id="us-gaap_RestrictedStockMember_lbl1">Restricted Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockMember" xlink:to="us-gaap_RestrictedStockMember_lbl1" xlink:title="label: RestrictedStockMember to us-gaap_RestrictedStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/verboseLabel" 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RetainedEarningsMember_lbl" xml:lang="en-US" id="us-gaap_RetainedEarningsMember_lbl">Accumulated Deficit [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RetainedEarningsMember_lbl1" xml:lang="en-US" id="us-gaap_RetainedEarningsMember_lbl1">Retained Earnings [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl1" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xml:lang="en-US" id="us-gaap_RetainedEarningsAccumulatedDeficit_lbl">Accumulated deficit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsAccumulatedDeficit" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xlink:title="label: RetainedEarningsAccumulatedDeficit to us-gaap_RetainedEarningsAccumulatedDeficit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xml:lang="en-US" id="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1">Retained Earnings (Accumulated Deficit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsAccumulatedDeficit" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xlink:title="label: RetainedEarningsAccumulatedDeficit to us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerMember" xlink:label="RevenueFromContractWithCustomerMember" xlink:title="RevenueFromContractWithCustomerMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl">Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl1">Revenue from Contract with Customer Benchmark [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl">Revenue Recognition [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1">Revenue from Contract with Customer [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:label="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:title="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl">Future Minimum Payments Under Operating Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:to="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl" xlink:title="label: ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock to us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl1">Schedule of Future Minimum Lease Payments for Capital Leases [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:to="us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl1" xlink:title="label: ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock to us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:label="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:title="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl">Basic and Diluted Net Income Per Share</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:to="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl" xlink:title="label: ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock to us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl1">Schedule of Earnings Per Share, Basic and Diluted [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:to="us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl1" xlink:title="label: ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock to us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:label="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:title="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl">Basic Net Income (Loss) per Share</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:to="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl" xlink:title="label: ScheduleOfEarningsPerShareBasicByCommonClassTextBlock to us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl1">Schedule of Earnings Per Share, Basic, by Common Class, Including Two Class Method [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:to="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl1" xlink:title="label: ScheduleOfEarningsPerShareBasicByCommonClassTextBlock to us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:label="ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:title="ScheduleOfSegmentReportingInformationBySegmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl">Segment Information</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:to="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl" xlink:title="label: ScheduleOfSegmentReportingInformationBySegmentTextBlock to us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1">Schedule of Segment Reporting Information, by Segment [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:to="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1" xlink:title="label: ScheduleOfSegmentReportingInformationBySegmentTextBlock to us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:label="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:title="ScheduleOfSegmentReportingInformationBySegmentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_lbl">Schedule of Segment Reporting Information, by Segment [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_lbl" xlink:title="label: ScheduleOfSegmentReportingInformationBySegmentTable to us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" xlink:title="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl" xml:lang="en-US" id="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl">Revenue from Collaborative Relationship</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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureTextBlock" xlink:label="SegmentReportingDisclosureTextBlock" xlink:title="SegmentReportingDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SegmentReportingDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_SegmentReportingDisclosureTextBlock_lbl">Segment Information</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingDisclosureTextBlock" xlink:to="us-gaap_SegmentReportingDisclosureTextBlock_lbl" xlink:title="label: SegmentReportingDisclosureTextBlock to us-gaap_SegmentReportingDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_SegmentReportingDisclosureTextBlock_lbl1">Segment Reporting Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingDisclosureTextBlock" xlink:to="us-gaap_SegmentReportingDisclosureTextBlock_lbl1" xlink:title="label: SegmentReportingDisclosureTextBlock to us-gaap_SegmentReportingDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingInformationLineItems" xlink:label="SegmentReportingInformationLineItems" xlink:title="SegmentReportingInformationLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingInformationLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingInformationLineItems_lbl" xml:lang="en-US" id="us-gaap_SegmentReportingInformationLineItems_lbl">Segment Reporting Information [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingInformationLineItems" xlink:to="us-gaap_SegmentReportingInformationLineItems_lbl" xlink:title="label: SegmentReportingInformationLineItems to us-gaap_SegmentReportingInformationLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl">Segment Information [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:to="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl" xlink:title="label: SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract to us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl1">Segment Reporting, Disclosure of Other Information about Entity's Reportable Segments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:to="us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl1" xlink:title="label: SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract to us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain" xlink:title="SegmentDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentDomain_lbl" xml:lang="en-US" id="us-gaap_SegmentDomain_lbl">Segments [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentDomain" xlink:to="us-gaap_SegmentDomain_lbl" xlink:title="label: SegmentDomain to us-gaap_SegmentDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingAbstract" xlink:label="SegmentReportingAbstract" xlink:title="SegmentReportingAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingAbstract_lbl" xml:lang="en-US" id="us-gaap_SegmentReportingAbstract_lbl">Segment Information [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingAbstract" xlink:to="us-gaap_SegmentReportingAbstract_lbl" xlink:title="label: SegmentReportingAbstract to us-gaap_SegmentReportingAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl">Selling, General and Administrative [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1">Selling, General and Administrative Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">Amendment to Equity Plan [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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 share-based awards and exercise of employee stock options (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xlink:title="label: SharesPaidForTaxWithholdingForShareBasedCompensation to us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1">Share-based Payment Arrangement, Shares Withheld for Tax Withholding Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: SharesPaidForTaxWithholdingForShareBasedCompensation to us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_SharesIssued_lbl" xml:lang="en-US" id="us-gaap_SharesIssued_lbl">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_SharesIssued_lbl1" xml:lang="en-US" id="us-gaap_SharesIssued_lbl1">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl1" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesIssued_lbl2" xml:lang="en-US" id="us-gaap_SharesIssued_lbl2">Shares, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl2" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:title="label: StatementOfFinancialPositionAbstract to us-gaap_StatementOfFinancialPositionAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="StatementClassOfStockAxis" xlink:title="StatementClassOfStockAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementClassOfStockAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementClassOfStockAxis_lbl" xml:lang="en-US" id="us-gaap_StatementClassOfStockAxis_lbl">Class of Stock [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementClassOfStockAxis" xlink:to="us-gaap_StatementClassOfStockAxis_lbl" xlink:title="label: StatementClassOfStockAxis to us-gaap_StatementClassOfStockAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementLineItems_lbl" xml:lang="en-US" id="us-gaap_StatementLineItems_lbl">Statement [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementLineItems" xlink:to="us-gaap_StatementLineItems_lbl" xlink:title="label: StatementLineItems to us-gaap_StatementLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementTable_lbl" xml:lang="en-US" id="us-gaap_StatementTable_lbl">Statement [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementTable" xlink:to="us-gaap_StatementTable_lbl" xlink:title="label: StatementTable to us-gaap_StatementTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementBusinessSegmentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementBusinessSegmentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementBusinessSegmentsAxis_lbl">Segments [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementBusinessSegmentsAxis" xlink:to="us-gaap_StatementBusinessSegmentsAxis_lbl" xlink:title="label: StatementBusinessSegmentsAxis to us-gaap_StatementBusinessSegmentsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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">CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl">Issuance of common stock in connection with employee stock plans</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1">Shares Issued, Value, Share-based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl">Issuance of common stock in connection with employee stock plans (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1">Shares Issued, Shares, Share-based Payment Arrangement, after Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockRepurchaseProgramAuthorizedAmount1" xlink:label="StockRepurchaseProgramAuthorizedAmount1" xlink:title="StockRepurchaseProgramAuthorizedAmount1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xml:lang="en-US" id="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl">Authorized amount of share repurchase program</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchaseProgramAuthorizedAmount1" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xlink:title="label: StockRepurchaseProgramAuthorizedAmount1 to us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1">Stock Repurchase Program, Authorized Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchaseProgramAuthorizedAmount1" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xlink:title="label: StockRepurchaseProgramAuthorizedAmount1 to us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="StockIssuedDuringPeriodSharesNewIssues" xlink:title="StockIssuedDuringPeriodSharesNewIssues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl">Biogen stock purchase (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xlink:title="label: StockIssuedDuringPeriodSharesNewIssues to us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1">Stock Issued During Period, Shares, New Issues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesNewIssues to us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="StockIssuedDuringPeriodValueNewIssues" xlink:title="StockIssuedDuringPeriodValueNewIssues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl">Biogen stock purchase</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" xlink:title="label: StockIssuedDuringPeriodValueNewIssues to us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1">Stock Issued During Period, Value, New Issues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" xlink:title="label: StockIssuedDuringPeriodValueNewIssues to us-gaap_StockIssuedDuringPeriodValueNewIssues_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockRepurchasedDuringPeriodShares" xlink:label="StockRepurchasedDuringPeriodShares" xlink:title="StockRepurchasedDuringPeriodShares" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xml:lang="en-US" id="us-gaap_StockRepurchasedDuringPeriodShares_lbl">Shares repurchased (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xlink:title="label: StockRepurchasedDuringPeriodShares to us-gaap_StockRepurchasedDuringPeriodShares_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchasedDuringPeriodShares_lbl1">Stock Repurchased During Period, Shares</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xlink:title="label: StockRepurchasedDuringPeriodShares to us-gaap_StockRepurchasedDuringPeriodShares_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 Ionis 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/totalLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl">Total stockholders' equity</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/periodEndLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2">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_lbl2" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl3" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl3">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_lbl3" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl3" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="SubsequentEventMember" xlink:title="SubsequentEventMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventMember_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventMember_lbl">Subsequent Event [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventMember" xlink:to="us-gaap_SubsequentEventMember_lbl" xlink:title="label: SubsequentEventMember to us-gaap_SubsequentEventMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeDomain_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventTypeDomain_lbl">Subsequent Event Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventTypeDomain_lbl" xlink:title="label: SubsequentEventTypeDomain to us-gaap_SubsequentEventTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeAxis_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventTypeAxis_lbl">Subsequent Event Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeAxis_lbl" xlink:title="label: SubsequentEventTypeAxis to us-gaap_SubsequentEventTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="TypeOfAdoptionMember" xlink:title="TypeOfAdoptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_TypeOfAdoptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_TypeOfAdoptionMember_lbl" xml:lang="en-US" id="us-gaap_TypeOfAdoptionMember_lbl">Type of Adoption [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TypeOfAdoptionMember" xlink:to="us-gaap_TypeOfAdoptionMember_lbl" xlink:title="label: TypeOfAdoptionMember to us-gaap_TypeOfAdoptionMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/label" 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/verboseLabel" 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 income (loss) per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingBasic" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xlink:title="label: WeightedAverageNumberOfSharesOutstandingBasic to us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1">Weighted average shares outstanding (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingBasic" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOutstandingBasic to us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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 income (loss) per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1">Shares used in computing diluted net income per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidatedEntitiesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidatedEntitiesDomain_lbl" xml:lang="en-US" id="srt_ConsolidatedEntitiesDomain_lbl">Consolidated Entities [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesDomain" xlink:to="srt_ConsolidatedEntitiesDomain_lbl" xlink:title="label: ConsolidatedEntitiesDomain to srt_ConsolidatedEntitiesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidatedEntitiesAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidatedEntitiesAxis_lbl" xml:lang="en-US" id="srt_ConsolidatedEntitiesAxis_lbl">Consolidated Entities [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesAxis" xlink:to="srt_ConsolidatedEntitiesAxis_lbl" xlink:title="label: ConsolidatedEntitiesAxis to srt_ConsolidatedEntitiesAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsDomain" xlink:label="ConsolidationItemsDomain" xlink:title="ConsolidationItemsDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidationItemsDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidationItemsDomain_lbl" xml:lang="en-US" id="srt_ConsolidationItemsDomain_lbl">Consolidation Items [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationItemsDomain" xlink:to="srt_ConsolidationItemsDomain_lbl" xlink:title="label: ConsolidationItemsDomain to srt_ConsolidationItemsDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsAxis" xlink:label="ConsolidationItemsAxis" xlink:title="ConsolidationItemsAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidationItemsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidationItemsAxis_lbl" xml:lang="en-US" id="srt_ConsolidationItemsAxis_lbl">Consolidation Items [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationItemsAxis" xlink:to="srt_ConsolidationItemsAxis_lbl" xlink:title="label: ConsolidationItemsAxis to srt_ConsolidationItemsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:label xlink:type="resource" xlink:label="srt_MajorCustomersAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MajorCustomersAxis_lbl" xml:lang="en-US" id="srt_MajorCustomersAxis_lbl">Customer [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MajorCustomersAxis" xlink:to="srt_MajorCustomersAxis_lbl" xlink:title="label: MajorCustomersAxis to srt_MajorCustomersAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:label xlink:type="resource" xlink:label="srt_OwnershipAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipAxis_lbl" xml:lang="en-US" id="srt_OwnershipAxis_lbl">Ownership [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OwnershipAxis" xlink:to="srt_OwnershipAxis_lbl" xlink:title="label: OwnershipAxis to srt_OwnershipAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:label xlink:type="resource" xlink:label="srt_OwnershipDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipDomain_lbl" xml:lang="en-US" id="srt_OwnershipDomain_lbl">Ownership [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OwnershipDomain" xlink:to="srt_OwnershipDomain_lbl" xlink:title="label: OwnershipDomain to srt_OwnershipDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ProductsAndServicesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductsAndServicesDomain_lbl" xml:lang="en-US" id="srt_ProductsAndServicesDomain_lbl">Products and Services [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductsAndServicesDomain" xlink:to="srt_ProductsAndServicesDomain_lbl" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis_lbl" xml:lang="en-US" id="srt_ProductOrServiceAxis_lbl">Products and Services [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductOrServiceAxis" xlink:to="srt_ProductOrServiceAxis_lbl" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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">Range [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeMember" xlink:to="srt_RangeMember_lbl" xlink:title="label: RangeMember to srt_RangeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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">Range [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeAxis" xlink:to="srt_RangeAxis_lbl" xlink:title="label: RangeAxis to srt_RangeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioUnspecifiedDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioUnspecifiedDomain_lbl" xml:lang="en-US" id="srt_ScenarioUnspecifiedDomain_lbl">Scenario [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioUnspecifiedDomain" xlink:to="srt_ScenarioUnspecifiedDomain_lbl" xlink:title="label: ScenarioUnspecifiedDomain to srt_ScenarioUnspecifiedDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioForecastMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioForecastMember_lbl" xml:lang="en-US" id="srt_ScenarioForecastMember_lbl">Forecast [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioForecastMember" xlink:to="srt_ScenarioForecastMember_lbl" xlink:title="label: ScenarioForecastMember to srt_ScenarioForecastMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:label xlink:type="resource" xlink:label="srt_StatementScenarioAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_StatementScenarioAxis_lbl" xml:lang="en-US" id="srt_StatementScenarioAxis_lbl">Scenario [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementScenarioAxis" xlink:to="srt_StatementScenarioAxis_lbl" xlink:title="label: StatementScenarioAxis to srt_StatementScenarioAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd#invest_InvestmentsScheduleAbstract" xlink:label="InvestmentsScheduleAbstract" xlink:title="InvestmentsScheduleAbstract" />
    <link:label xlink:type="resource" xlink:label="invest_InvestmentsScheduleAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="invest_InvestmentsScheduleAbstract_lbl" xml:lang="en-US" id="invest_InvestmentsScheduleAbstract_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="InvestmentsScheduleAbstract" xlink:to="invest_InvestmentsScheduleAbstract_lbl" xlink:title="label: InvestmentsScheduleAbstract to invest_InvestmentsScheduleAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="invest_InvestmentsScheduleAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="invest_InvestmentsScheduleAbstract_lbl1" xml:lang="en-US" id="invest_InvestmentsScheduleAbstract_lbl1">Investments Schedule [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsScheduleAbstract" xlink:to="invest_InvestmentsScheduleAbstract_lbl1" xlink:title="label: InvestmentsScheduleAbstract to invest_InvestmentsScheduleAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd#invest_InvestmentTextBlock" xlink:label="InvestmentTextBlock" xlink:title="InvestmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="invest_InvestmentTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="invest_InvestmentTextBlock_lbl" xml:lang="en-US" id="invest_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="invest_InvestmentTextBlock_lbl" xlink:title="label: InvestmentTextBlock to invest_InvestmentTextBlock_lbl" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl">Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1">Royalty percentage received on net sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2">Royalty percentage received on net sales of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfDrug to ions_RoyaltyPercentageReceivedOnNetSalesOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl">The maximum amount of payments receivable for development, regulatory and sales milestones under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1">Maximum amount of payments receivable for development, regulatory and sales milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2">Maximum amount of payments receivable for development, regulatory and sales milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones to ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_UpfrontLicenseFeeToBeReceived" xlink:label="UpfrontLicenseFeeToBeReceived" xlink:title="UpfrontLicenseFeeToBeReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontLicenseFeeToBeReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontLicenseFeeToBeReceived_lbl" xml:lang="en-US" id="ions_UpfrontLicenseFeeToBeReceived_lbl">The amount of upfront license fees expected to be received under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontLicenseFeeToBeReceived" xlink:to="ions_UpfrontLicenseFeeToBeReceived_lbl" xlink:title="label: UpfrontLicenseFeeToBeReceived to ions_UpfrontLicenseFeeToBeReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontLicenseFeeToBeReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontLicenseFeeToBeReceived_lbl1" xml:lang="en-US" id="ions_UpfrontLicenseFeeToBeReceived_lbl1">Upfront license fee to be received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontLicenseFeeToBeReceived" xlink:to="ions_UpfrontLicenseFeeToBeReceived_lbl1" xlink:title="label: UpfrontLicenseFeeToBeReceived to ions_UpfrontLicenseFeeToBeReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontLicenseFeeToBeReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontLicenseFeeToBeReceived_lbl2" xml:lang="en-US" id="ions_UpfrontLicenseFeeToBeReceived_lbl2">Upfront license fee to be received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontLicenseFeeToBeReceived" xlink:to="ions_UpfrontLicenseFeeToBeReceived_lbl2" xlink:title="label: UpfrontLicenseFeeToBeReceived to ions_UpfrontLicenseFeeToBeReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Pfizer for the license of AKCEA-ANGPTL3-LR to treat people with cardiovascular and metabolic diseases..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in October 2019 with Pfizer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2">Pfizer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseInformationTableTextBlock" xlink:label="LesseeOperatingLeaseInformationTableTextBlock" xlink:title="LesseeOperatingLeaseInformationTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl">Tabular disclosure of information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1">Lessee, Operating Lease Information [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2">Amounts Related to Operating Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:label="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:title="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl" xml:lang="en-US" id="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl">Office and laboratory space in a facility adjacent to the Company's manufacturing facility leased under non-cancelable operating leases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:to="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl" xlink:title="label: OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember to ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl1" xml:lang="en-US" id="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl1">Office and Laboratory Space Adjacent to Manufacturing Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:to="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl1" xlink:title="label: OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember to ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl2" xml:lang="en-US" id="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl2">Office and Laboratory Space Adjacent to Manufacturing Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:to="ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl2" xlink:title="label: OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember to ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:label="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:title="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl" xml:lang="en-US" id="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl">Office space subleased to Akcea Therapeutics, Inc. (Akcea) leased under non-cancelable operating leases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:to="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl" xlink:title="label: OfficeSpaceSubleasedToAkceaTherapeuticsIncMember to ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl1" xml:lang="en-US" id="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl1">Office Space Subleased to Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:to="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl1" xlink:title="label: OfficeSpaceSubleasedToAkceaTherapeuticsIncMember to ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl2" xml:lang="en-US" id="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl2">Office Space Subleased to Akcea [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:to="ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl2" xlink:title="label: OfficeSpaceSubleasedToAkceaTherapeuticsIncMember to ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeSpaceForCorporateHeadquartersMember" xlink:label="OfficeSpaceForCorporateHeadquartersMember" xlink:title="OfficeSpaceForCorporateHeadquartersMember" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceForCorporateHeadquartersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OfficeSpaceForCorporateHeadquartersMember_lbl" xml:lang="en-US" id="ions_OfficeSpaceForCorporateHeadquartersMember_lbl">Office space located in Boston, Massachusetts for Akcea Therapeutics, Inc.'s corporate headquarters leased under non-cancelable operating leases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceForCorporateHeadquartersMember" xlink:to="ions_OfficeSpaceForCorporateHeadquartersMember_lbl" xlink:title="label: OfficeSpaceForCorporateHeadquartersMember to ions_OfficeSpaceForCorporateHeadquartersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OfficeSpaceForCorporateHeadquartersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OfficeSpaceForCorporateHeadquartersMember_lbl1" xml:lang="en-US" id="ions_OfficeSpaceForCorporateHeadquartersMember_lbl1">Office Space for Corporate Headquarters [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OfficeSpaceForCorporateHeadquartersMember" xlink:to="ions_OfficeSpaceForCorporateHeadquartersMember_lbl1" xlink:title="label: OfficeSpaceForCorporateHeadquartersMember to ions_OfficeSpaceForCorporateHeadquartersMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl">Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the fifth anniversary of the rent commencement date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1">Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Fifth Anniversary of Rent Commencement Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2">Letter of credit on fifth anniversary of rent commencement date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:label="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl">Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1">Lessee, Operating Lease, Initial Letter of Credit to Secure Lease Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2">Initial amount of letter of credit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:to="ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" xlink:title="label: LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation to ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl">Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1">Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Third Anniversary of Rent Commencement Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2">Letter of credit on third anniversary of rent commencement date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:to="ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" xlink:title="label: LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate to ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:label="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessee's operating leasing arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1">Lessee, Leasing Arrangements, Operating Leases, Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xml:lang="en-US" id="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2">Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:to="ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" xlink:title="label: LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease to ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:label="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="LesseeOperatingLeaseAllowanceForTenantImprovements" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl">Allowance for tenant improvements to the office space included in the lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1">Lessee, Operating Lease, Allowance for Tenant Improvements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2">Tenant improvement allowance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:to="ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" xlink:title="label: LesseeOperatingLeaseAllowanceForTenantImprovements to ions_LesseeOperatingLeaseAllowanceForTenantImprovements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:label="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="LesseeOperatingLeasePeriodOfFreeRent" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl">Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1">Lessee, Operating Lease, Period of Free Rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2">Period of free rent under lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl">Disclosure of information about collaborative arrangements and non-collaborative arrangement transactions.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentServicesMember" xlink:label="ResearchAndDevelopmentServicesMember" xlink:title="ResearchAndDevelopmentServicesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesMember_lbl">Research and development services performed under a collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesMember" xlink:to="ions_ResearchAndDevelopmentServicesMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesMember to ions_ResearchAndDevelopmentServicesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesMember_lbl1">Research and Development Services [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesMember" xlink:to="ions_ResearchAndDevelopmentServicesMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesMember to ions_ResearchAndDevelopmentServicesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesMember_lbl2">R&amp;D Services [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesMember" xlink:to="ions_ResearchAndDevelopmentServicesMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesMember to ions_ResearchAndDevelopmentServicesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2012. This agreement is focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases (Neurology).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2">2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfNewTargetsAdvanced" xlink:label="NumberOfNewTargetsAdvanced" xlink:title="NumberOfNewTargetsAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfNewTargetsAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfNewTargetsAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfNewTargetsAdvanced_lbl">The number of new targets advanced 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="NumberOfNewTargetsAdvanced" xlink:to="ions_NumberOfNewTargetsAdvanced_lbl" xlink:title="label: NumberOfNewTargetsAdvanced to ions_NumberOfNewTargetsAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfNewTargetsAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfNewTargetsAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfNewTargetsAdvanced_lbl1">Number of new targets advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfNewTargetsAdvanced" xlink:to="ions_NumberOfNewTargetsAdvanced_lbl1" xlink:title="label: NumberOfNewTargetsAdvanced to ions_NumberOfNewTargetsAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfNewTargetsAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfNewTargetsAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfNewTargetsAdvanced_lbl2">Number of new targets advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfNewTargetsAdvanced" xlink:to="ions_NumberOfNewTargetsAdvanced_lbl2" xlink:title="label: NumberOfNewTargetsAdvanced to ions_NumberOfNewTargetsAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfMilestonePaymentsAchieved" xlink:label="NumberOfMilestonePaymentsAchieved" xlink:title="NumberOfMilestonePaymentsAchieved" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMilestonePaymentsAchieved_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMilestonePaymentsAchieved_lbl" xml:lang="en-US" id="ions_NumberOfMilestonePaymentsAchieved_lbl">The number of milestone payments achieved 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="NumberOfMilestonePaymentsAchieved" xlink:to="ions_NumberOfMilestonePaymentsAchieved_lbl" xlink:title="label: NumberOfMilestonePaymentsAchieved to ions_NumberOfMilestonePaymentsAchieved_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMilestonePaymentsAchieved_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMilestonePaymentsAchieved_lbl1" xml:lang="en-US" id="ions_NumberOfMilestonePaymentsAchieved_lbl1">Number of milestone payments achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMilestonePaymentsAchieved" xlink:to="ions_NumberOfMilestonePaymentsAchieved_lbl1" xlink:title="label: NumberOfMilestonePaymentsAchieved to ions_NumberOfMilestonePaymentsAchieved_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMilestonePaymentsAchieved_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMilestonePaymentsAchieved_lbl2" xml:lang="en-US" id="ions_NumberOfMilestonePaymentsAchieved_lbl2">Number of milestone payments achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMilestonePaymentsAchieved" xlink:to="ions_NumberOfMilestonePaymentsAchieved_lbl2" xlink:title="label: NumberOfMilestonePaymentsAchieved to ions_NumberOfMilestonePaymentsAchieved_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:label="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:title="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl" xml:lang="en-US" id="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl">The number of medicines currently in development under collaborations.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:to="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl" xlink:title="label: NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations to ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl1" xml:lang="en-US" id="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl1">Number of medicines currently in development under collaborations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:to="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl1" xlink:title="label: NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations to ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl2" xml:lang="en-US" id="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl2">Number of medicines currently in development under collaborations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:to="ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl2" xlink:title="label: NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations to ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Biogen Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1">Collaborative Arrangements and Licensing Agreements, Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISMAPTMember" xlink:label="IONISMAPTMember" xlink:title="IONISMAPTMember" />
    <link:label xlink:type="resource" xlink:label="ions_IONISMAPTMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISMAPTMember_lbl" xml:lang="en-US" id="ions_IONISMAPTMember_lbl">IONIS-MAPT is an antisense drug designed to selectively reduce the production of microtubule-associated protein tau (MAPT), or tau protein, in the brain, for the treatment of Alzheimer's disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISMAPTMember" xlink:to="ions_IONISMAPTMember_lbl" xlink:title="label: IONISMAPTMember to ions_IONISMAPTMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISMAPTMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISMAPTMember_lbl1" xml:lang="en-US" id="ions_IONISMAPTMember_lbl1">IONIS-MAPT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISMAPTMember" xlink:to="ions_IONISMAPTMember_lbl1" xlink:title="label: IONISMAPTMember to ions_IONISMAPTMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISMAPTMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISMAPTMember_lbl2" xml:lang="en-US" id="ions_IONISMAPTMember_lbl2">IONIS-MAPT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISMAPTMember" xlink:to="ions_IONISMAPTMember_lbl2" xlink:title="label: IONISMAPTMember to ions_IONISMAPTMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:label="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="UpfrontPaymentReceivedIncludingPurchaseOfStock" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl">The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1">Upfront payment received, including purchase of stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MilestonePaymentsReceived" xlink:label="MilestonePaymentsReceived" xlink:title="MilestonePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentsReceived_lbl" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl">The amount of milestone payments received during the period under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentsReceived_lbl1" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl1">Milestone payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl1" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_MilestonePaymentsReceived_lbl2" xml:lang="en-US" id="ions_MilestonePaymentsReceived_lbl2">Milestone payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsReceived" xlink:to="ions_MilestonePaymentsReceived_lbl2" xlink:title="label: MilestonePaymentsReceived to ions_MilestonePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:label="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="PaymentsIncludedInTransactionPriceForPerformanceObligation" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xml:lang="en-US" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl">Total payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:title="label: PaymentsIncludedInTransactionPriceForPerformanceObligation to ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xml:lang="en-US" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1">Payments included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:title="label: PaymentsIncludedInTransactionPriceForPerformanceObligation to ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xml:lang="en-US" id="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2">Payments included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:title="label: PaymentsIncludedInTransactionPriceForPerformanceObligation to ions_PaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2">New Antisense Medicines for the Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1">Collaborative Arrangements and Licensing Agreements, Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2">Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsRocheMember to ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisHttMember" xlink:label="IonisHttMember" xlink:title="IonisHttMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisHttMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisHttMember_lbl" xml:lang="en-US" id="ions_IonisHttMember_lbl">An antisense drug targeting huntingtin, or HTT, protein.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisHttMember" xlink:to="ions_IonisHttMember_lbl" xlink:title="label: IonisHttMember to ions_IonisHttMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisHttMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisHttMember_lbl1" xml:lang="en-US" id="ions_IonisHttMember_lbl1">IONIS-HTT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisHttMember" xlink:to="ions_IonisHttMember_lbl1" xlink:title="label: IonisHttMember to ions_IonisHttMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisHttMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisHttMember_lbl2" xml:lang="en-US" id="ions_IonisHttMember_lbl2">IONIS-HTT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisHttMember" xlink:to="ions_IonisHttMember_lbl2" xlink:title="label: IonisHttMember to ions_IonisHttMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfCollaborationAgreements" xlink:label="NumberOfCollaborationAgreements" xlink:title="NumberOfCollaborationAgreements" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfCollaborationAgreements_lbl" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl">The number of collaboration agreements with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfCollaborationAgreements_lbl1" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl1">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl1" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfCollaborationAgreements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfCollaborationAgreements_lbl2" xml:lang="en-US" id="ions_NumberOfCollaborationAgreements_lbl2">Number of collaboration agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfCollaborationAgreements" xlink:to="ions_NumberOfCollaborationAgreements_lbl2" xlink:title="label: NumberOfCollaborationAgreements to ions_NumberOfCollaborationAgreements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AKCEAAPOALMember" xlink:label="AKCEAAPOALMember" xlink:title="AKCEAAPOALMember" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOALMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AKCEAAPOALMember_lbl" xml:lang="en-US" id="ions_AKCEAAPOALMember_lbl">An antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOALMember" xlink:to="ions_AKCEAAPOALMember_lbl" xlink:title="label: AKCEAAPOALMember to ions_AKCEAAPOALMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOALMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AKCEAAPOALMember_lbl1" xml:lang="en-US" id="ions_AKCEAAPOALMember_lbl1">AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOALMember" xlink:to="ions_AKCEAAPOALMember_lbl1" xlink:title="label: AKCEAAPOALMember to ions_AKCEAAPOALMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AKCEAAPOALMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AKCEAAPOALMember_lbl2" xml:lang="en-US" id="ions_AKCEAAPOALMember_lbl2">AKCEA-APO(a)-L [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AKCEAAPOALMember" xlink:to="ions_AKCEAAPOALMember_lbl2" xlink:title="label: AKCEAAPOALMember to ions_AKCEAAPOALMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_SublicenseFeePaidForLicenseOfDrug" xlink:label="SublicenseFeePaidForLicenseOfDrug" xlink:title="SublicenseFeePaidForLicenseOfDrug" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseFeePaidForLicenseOfDrug_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SublicenseFeePaidForLicenseOfDrug_lbl" xml:lang="en-US" id="ions_SublicenseFeePaidForLicenseOfDrug_lbl">The amount of the sublicense fee paid in common stock.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseFeePaidForLicenseOfDrug" xlink:to="ions_SublicenseFeePaidForLicenseOfDrug_lbl" xlink:title="label: SublicenseFeePaidForLicenseOfDrug to ions_SublicenseFeePaidForLicenseOfDrug_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseFeePaidForLicenseOfDrug_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SublicenseFeePaidForLicenseOfDrug_lbl1" xml:lang="en-US" id="ions_SublicenseFeePaidForLicenseOfDrug_lbl1">Sublicense fee paid for license of drug</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseFeePaidForLicenseOfDrug" xlink:to="ions_SublicenseFeePaidForLicenseOfDrug_lbl1" xlink:title="label: SublicenseFeePaidForLicenseOfDrug to ions_SublicenseFeePaidForLicenseOfDrug_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SublicenseFeePaidForLicenseOfDrug_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SublicenseFeePaidForLicenseOfDrug_lbl2" xml:lang="en-US" id="ions_SublicenseFeePaidForLicenseOfDrug_lbl2">Sublicense fee paid in stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SublicenseFeePaidForLicenseOfDrug" xlink:to="ions_SublicenseFeePaidForLicenseOfDrug_lbl2" xlink:title="label: SublicenseFeePaidForLicenseOfDrug to ions_SublicenseFeePaidForLicenseOfDrug_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:label xlink:type="resource" xlink:label="ions_ReceiptOfSharesInSubsidiary_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ReceiptOfSharesInSubsidiary_lbl" xml:lang="en-US" id="ions_ReceiptOfSharesInSubsidiary_lbl">The number of shares received from the subsidiary during the period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceiptOfSharesInSubsidiary" xlink:to="ions_ReceiptOfSharesInSubsidiary_lbl" xlink:title="label: ReceiptOfSharesInSubsidiary to ions_ReceiptOfSharesInSubsidiary_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ReceiptOfSharesInSubsidiary_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ReceiptOfSharesInSubsidiary_lbl1" xml:lang="en-US" id="ions_ReceiptOfSharesInSubsidiary_lbl1">Receipt of shares in subsidiary</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceiptOfSharesInSubsidiary" xlink:to="ions_ReceiptOfSharesInSubsidiary_lbl1" xlink:title="label: ReceiptOfSharesInSubsidiary to ions_ReceiptOfSharesInSubsidiary_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ReceiptOfSharesInSubsidiary_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ReceiptOfSharesInSubsidiary_lbl2" xml:lang="en-US" id="ions_ReceiptOfSharesInSubsidiary_lbl2">Additional shares of Akcea stock received (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceiptOfSharesInSubsidiary" xlink:to="ions_ReceiptOfSharesInSubsidiary_lbl2" xlink:title="label: ReceiptOfSharesInSubsidiary to ions_ReceiptOfSharesInSubsidiary_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MilestonePaymentEarned" xlink:label="MilestonePaymentEarned" xlink:title="MilestonePaymentEarned" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentEarned_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentEarned_lbl" xml:lang="en-US" id="ions_MilestonePaymentEarned_lbl">Milestone payment earned during the period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentEarned" xlink:to="ions_MilestonePaymentEarned_lbl" xlink:title="label: MilestonePaymentEarned to ions_MilestonePaymentEarned_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentEarned_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentEarned_lbl1" xml:lang="en-US" id="ions_MilestonePaymentEarned_lbl1">Milestone payment earned</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentEarned" xlink:to="ions_MilestonePaymentEarned_lbl1" xlink:title="label: MilestonePaymentEarned to ions_MilestonePaymentEarned_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:label="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="WeightedAverageNumberOfSharesOwnedInSubsidiary" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl">Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1">Weighted average number of shares owned in subsidiary</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xml:lang="en-US" id="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2">Weighted average shares owned in Akcea (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:to="ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" xlink:title="label: WeightedAverageNumberOfSharesOwnedInSubsidiary to ions_WeightedAverageNumberOfSharesOwnedInSubsidiary_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl">Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1">Incremental Common Shares Attributable to Employee Stock Purchase Plan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2">Shares issuable related to our Employee Stock Purchase Plan (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsMember" xlink:label="AkceaTherapeuticsMember" xlink:title="AkceaTherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl">Reportable segment which includes the operations of the Company's wholly-owned subsidiary, Akcea Therapeutics, Inc., which was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl1">Akcea Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl1" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaTherapeuticsMember_lbl2" xml:lang="en-US" id="ions_AkceaTherapeuticsMember_lbl2">Akcea Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsMember" xlink:to="ions_AkceaTherapeuticsMember_lbl2" xlink:title="label: AkceaTherapeuticsMember to ions_AkceaTherapeuticsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisCoreMember_lbl" xml:lang="en-US" id="ions_IonisCoreMember_lbl">Reportable segment in which the Company is exploiting a novel drug discovery platform created to generate a broad pipeline of first-in-class or best-in-class drugs for the Company and its partners. This segment generates revenue from a multifaceted partnering strategy. This strategy includes revenue from collaborations with preferred partners, traditional alliances and working with a consortium of companies that can exploit the Company's drugs and technology. Revenue from collaborations with preferred partners and traditional alliances may consist of upfront payments, milestone payments, licensing fees and royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisCoreMember_lbl1" xml:lang="en-US" id="ions_IonisCoreMember_lbl1">Ionis Core [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl1" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_IonisCoreMember_lbl2" xml:lang="en-US" id="ions_IonisCoreMember_lbl2">Ionis Core [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl2" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisCoreMember_lbl3" xml:lang="en-US" id="ions_IonisCoreMember_lbl3">Ionis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisCoreMember" xlink:to="ions_IonisCoreMember_lbl3" xlink:title="label: IonisCoreMember to ions_IonisCoreMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CostOfProductsSoldPreviouslyRecognized" xlink:label="CostOfProductsSoldPreviouslyRecognized" xlink:title="CostOfProductsSoldPreviouslyRecognized" />
    <link:label xlink:type="resource" xlink:label="ions_CostOfProductsSoldPreviouslyRecognized_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CostOfProductsSoldPreviouslyRecognized_lbl" xml:lang="en-US" id="ions_CostOfProductsSoldPreviouslyRecognized_lbl">The costs related to goods produced and sold that were previously recognized as expense and are related to the commercial revenue recognized during the period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfProductsSoldPreviouslyRecognized" xlink:to="ions_CostOfProductsSoldPreviouslyRecognized_lbl" xlink:title="label: CostOfProductsSoldPreviouslyRecognized to ions_CostOfProductsSoldPreviouslyRecognized_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CostOfProductsSoldPreviouslyRecognized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CostOfProductsSoldPreviouslyRecognized_lbl1" xml:lang="en-US" id="ions_CostOfProductsSoldPreviouslyRecognized_lbl1">Cost of Products Sold Previously Recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfProductsSoldPreviouslyRecognized" xlink:to="ions_CostOfProductsSoldPreviouslyRecognized_lbl1" xlink:title="label: CostOfProductsSoldPreviouslyRecognized to ions_CostOfProductsSoldPreviouslyRecognized_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CostOfProductsSoldPreviouslyRecognized_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CostOfProductsSoldPreviouslyRecognized_lbl2" xml:lang="en-US" id="ions_CostOfProductsSoldPreviouslyRecognized_lbl2">Previously expensed costs to produce TEGSEDI related to TEGSEDI commercial revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfProductsSoldPreviouslyRecognized" xlink:to="ions_CostOfProductsSoldPreviouslyRecognized_lbl2" xlink:title="label: CostOfProductsSoldPreviouslyRecognized to ions_CostOfProductsSoldPreviouslyRecognized_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPotentialMilestonePayment_lbl" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl">The next potential milestone 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="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPotentialMilestonePayment_lbl1" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl1">Next potential milestone payment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl1" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPotentialMilestonePayment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPotentialMilestonePayment_lbl2" xml:lang="en-US" id="ions_NextPotentialMilestonePayment_lbl2">Next prospective milestone</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPotentialMilestonePayment" xlink:to="ions_NextPotentialMilestonePayment_lbl2" xlink:title="label: NextPotentialMilestonePayment to ions_NextPotentialMilestonePayment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_NumberOfDrugsCurrentlyBeingAdvanced" xlink:label="NumberOfDrugsCurrentlyBeingAdvanced" xlink:title="NumberOfDrugsCurrentlyBeingAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl">The number of drugs currently being advanced under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsCurrentlyBeingAdvanced" xlink:to="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" xlink:title="label: NumberOfDrugsCurrentlyBeingAdvanced to ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1">Number of drugs currently being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsCurrentlyBeingAdvanced" xlink:to="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" xlink:title="label: NumberOfDrugsCurrentlyBeingAdvanced to ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2">Number of drugs being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDrugsCurrentlyBeingAdvanced" xlink:to="ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" xlink:title="label: NumberOfDrugsCurrentlyBeingAdvanced to ions_NumberOfDrugsCurrentlyBeingAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISLRRK2Member" xlink:label="IONISLRRK2Member" xlink:title="IONISLRRK2Member" />
    <link:label xlink:type="resource" xlink:label="ions_IONISLRRK2Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IONISLRRK2Member_lbl" xml:lang="en-US" id="ions_IONISLRRK2Member_lbl">ONIS-LRRK2Rx (BIIB094) is an antisense drug for the treatment of people with Parkinson's disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISLRRK2Member" xlink:to="ions_IONISLRRK2Member_lbl" xlink:title="label: IONISLRRK2Member to ions_IONISLRRK2Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IONISLRRK2Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IONISLRRK2Member_lbl1" xml:lang="en-US" id="ions_IONISLRRK2Member_lbl1">IONIS-LRRK2 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISLRRK2Member" xlink:to="ions_IONISLRRK2Member_lbl1" xlink:title="label: IONISLRRK2Member to ions_IONISLRRK2Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IONISLRRK2Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IONISLRRK2Member_lbl2" xml:lang="en-US" id="ions_IONISLRRK2Member_lbl2">IONIS-LRRK2 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IONISLRRK2Member" xlink:to="ions_IONISLRRK2Member_lbl2" xlink:title="label: IONISLRRK2Member to ions_IONISLRRK2Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in September 2013. This agreement is a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases (Strategic Neurology).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2">2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl">Represents information pertaining to the collaborative arrangement and licensing agreement entered into with GlaxoSmithKline (GSK) in March 2010 to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2">GSK [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl">Represents information pertaining to collaborative arrangement entered into with Bayer HealthCare in May 2015 to develop and commercialize IONIS-FXI for the prevention of thrombosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2">Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl">Represents information pertaining to collaborative arrangement with Bayer HealthCare amended in February 2017 to advance IONIS-FXIRx for the prevention of thrombosis and to initiate development of IONIS-FXI-LRx.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1">Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2">Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBayerMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Bayer HealthCare.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1">Collaborative Arrangements and Licensing Agreements, Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2">Bayer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsBayerMember to ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl">Represents information pertaining to the expanded collaborative arrangement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2">2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl">Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Novartis to develop and commercialize AKCEA-APO(a)-L and AKCEA-APOCIII-L.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-LRx for the treatment of complement-mediated diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2">IONIS-FB-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in April 2013 to develop treatments for Huntington's disease, or HD, based on the Company's antisense technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2">Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl3" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl3">Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl3" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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 earned and amortized over period of performance</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-20190930.xsd#ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:label="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl">The number of performance obligations at the inception of a contract.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:to="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract to ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1">Revenue from Contract with Customer, Number of performance obligations at inception of contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:to="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract to ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2">Number of performance obligations at inception of contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:to="ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" xlink:title="label: RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract to ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl">Represents information pertaining to the collaborative arrangement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1">Collaborative Arrangement and Licensing Agreement Entered Into in March 2004 with Alnylam Pharmaceuticals, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" xlink:title="label: CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember to ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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-20190930.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-20190930.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-20190930.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-20190930.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/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2">Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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-20190930.xsd#ions_NovartisInternationalAGMember" xlink:label="NovartisInternationalAGMember" xlink:title="NovartisInternationalAGMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisInternationalAGMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisInternationalAGMember_lbl" xml:lang="en-US" id="ions_NovartisInternationalAGMember_lbl">Novartis International AG is a Swiss multinational pharmaceutical company based in Basel, Switzerland.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisInternationalAGMember" xlink:to="ions_NovartisInternationalAGMember_lbl" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisInternationalAGMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisInternationalAGMember_lbl1" xml:lang="en-US" id="ions_NovartisInternationalAGMember_lbl1">Novartis International AG [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisInternationalAGMember" xlink:to="ions_NovartisInternationalAGMember_lbl1" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisInternationalAGMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisInternationalAGMember_lbl2" xml:lang="en-US" id="ions_NovartisInternationalAGMember_lbl2">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisInternationalAGMember" xlink:to="ions_NovartisInternationalAGMember_lbl2" xlink:title="label: NovartisInternationalAGMember to ions_NovartisInternationalAGMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_OperatingLeaseRightOfUseAssetAmortization" xlink:label="OperatingLeaseRightOfUseAssetAmortization" xlink:title="OperatingLeaseRightOfUseAssetAmortization" />
    <link:label xlink:type="resource" xlink:label="ions_OperatingLeaseRightOfUseAssetAmortization_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OperatingLeaseRightOfUseAssetAmortization_lbl" xml:lang="en-US" id="ions_OperatingLeaseRightOfUseAssetAmortization_lbl">Amount of amortization expense attributable to right-of-use asset from operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortization" xlink:to="ions_OperatingLeaseRightOfUseAssetAmortization_lbl" xlink:title="label: OperatingLeaseRightOfUseAssetAmortization to ions_OperatingLeaseRightOfUseAssetAmortization_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OperatingLeaseRightOfUseAssetAmortization_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OperatingLeaseRightOfUseAssetAmortization_lbl1" xml:lang="en-US" id="ions_OperatingLeaseRightOfUseAssetAmortization_lbl1">Operating Lease, Right-of-Use Asset, Amortization</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortization" xlink:to="ions_OperatingLeaseRightOfUseAssetAmortization_lbl1" xlink:title="label: OperatingLeaseRightOfUseAssetAmortization to ions_OperatingLeaseRightOfUseAssetAmortization_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OperatingLeaseRightOfUseAssetAmortization_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OperatingLeaseRightOfUseAssetAmortization_lbl2" xml:lang="en-US" id="ions_OperatingLeaseRightOfUseAssetAmortization_lbl2">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="OperatingLeaseRightOfUseAssetAmortization" xlink:to="ions_OperatingLeaseRightOfUseAssetAmortization_lbl2" xlink:title="label: OperatingLeaseRightOfUseAssetAmortization to ions_OperatingLeaseRightOfUseAssetAmortization_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_PaymentsToAcquireLicensesAndOtherAssets" xlink:label="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="PaymentsToAcquireLicensesAndOtherAssets" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" xml:lang="en-US" id="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl">The cash outflow for acquisition of licenses and other assets not otherwise defined in the taxonomy.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireLicensesAndOtherAssets" xlink:to="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" xlink:title="label: PaymentsToAcquireLicensesAndOtherAssets to ions_PaymentsToAcquireLicensesAndOtherAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" xml:lang="en-US" id="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1">Payments to Acquire Licenses and Other Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireLicensesAndOtherAssets" xlink:to="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" xlink:title="label: PaymentsToAcquireLicensesAndOtherAssets to ions_PaymentsToAcquireLicensesAndOtherAssets_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" xml:lang="en-US" id="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2">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="PaymentsToAcquireLicensesAndOtherAssets" xlink:to="ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" xlink:title="label: PaymentsToAcquireLicensesAndOtherAssets to ions_PaymentsToAcquireLicensesAndOtherAssets_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:label="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="IncreaseDecreaseInAccruedAndDeferredLiabilities" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl">The increase (decrease) during the reporting period in the aggregate amount of expenses incurred but not yet paid and deferred liabilities due within one year or operating cycle.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" xlink:title="label: IncreaseDecreaseInAccruedAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1">Increase (Decrease) in Accrued and Deferred Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInAccruedAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" xml:lang="en-US" id="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2">Accrued liabilities and deferred rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:to="ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" xlink:title="label: IncreaseDecreaseInAccruedAndDeferredLiabilities to ions_IncreaseDecreaseInAccruedAndDeferredLiabilities_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl">Revenue from research and development services performed under a collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1">Research and Development Revenue Under Collaborative Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2">R&amp;D Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3">R&amp;D Revenue Under Collaborative Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:to="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl3" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl3">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_lbl3" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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-20190930.xsd#ions_NumberOfExecutiveOfficersTerminatingEmployment" xlink:label="NumberOfExecutiveOfficersTerminatingEmployment" xlink:title="NumberOfExecutiveOfficersTerminatingEmployment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl">The number of executive officers terminating employment with the company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatingEmployment" xlink:to="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" xlink:title="label: NumberOfExecutiveOfficersTerminatingEmployment to ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1">Number of executive officers terminating employment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatingEmployment" xlink:to="ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" xlink:title="label: NumberOfExecutiveOfficersTerminatingEmployment to ions_NumberOfExecutiveOfficersTerminatingEmployment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_EmployeeMember" xlink:label="EmployeeMember" xlink:title="EmployeeMember" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeMember_lbl" xml:lang="en-US" id="ions_EmployeeMember_lbl">Persons hired to provide services to a company on a regular basis in exchange for compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeMember" xlink:to="ions_EmployeeMember_lbl" xlink:title="label: EmployeeMember to ions_EmployeeMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeMember_lbl1" xml:lang="en-US" id="ions_EmployeeMember_lbl1">Employee [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeMember" xlink:to="ions_EmployeeMember_lbl1" xlink:title="label: EmployeeMember to ions_EmployeeMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeMember_lbl2" xml:lang="en-US" id="ions_EmployeeMember_lbl2">Employees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeMember" xlink:to="ions_EmployeeMember_lbl2" xlink:title="label: EmployeeMember to ions_EmployeeMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_BoardOfDirectorsMember" xlink:label="BoardOfDirectorsMember" xlink:title="BoardOfDirectorsMember" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BoardOfDirectorsMember_lbl" xml:lang="en-US" id="ions_BoardOfDirectorsMember_lbl">A group of individuals that are elected as, or elected to act as, representatives of the stockholders to establish corporate management related policies and to make decisions on major company issues.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorsMember" xlink:to="ions_BoardOfDirectorsMember_lbl" xlink:title="label: BoardOfDirectorsMember to ions_BoardOfDirectorsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BoardOfDirectorsMember_lbl1" xml:lang="en-US" id="ions_BoardOfDirectorsMember_lbl1">Board of Directors [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorsMember" xlink:to="ions_BoardOfDirectorsMember_lbl1" xlink:title="label: BoardOfDirectorsMember to ions_BoardOfDirectorsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_BoardOfDirectorStockOptionMember" xlink:label="BoardOfDirectorStockOptionMember" xlink:title="BoardOfDirectorStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl">An arrangement whereby a member of the Board of Directors is entitled to receive in the future, subject to vesting and other restrictions, a number of shares in the entity at a specified price, as defined in the agreement, as a form of compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl1" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl1">Board of Director Stock Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl2" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl2">Board of Director Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl2" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_EquityIncentivePlan2011Member" xlink:label="EquityIncentivePlan2011Member" xlink:title="EquityIncentivePlan2011Member" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquityIncentivePlan2011Member_lbl" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl">Represents the stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to employees, directors, and consultants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquityIncentivePlan2011Member_lbl1" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl1">Equity Incentive Plan 2011 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl1" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquityIncentivePlan2011Member_lbl2" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl2">2011 Equity Incentive Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl2" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl1">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl2">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl1">Convertible Senior Notes 1 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1 Percent Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">1 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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-20190930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond two years but within three 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="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after Two Through Three Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2">After two years but within three years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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-20190930.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-20190930.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/terseLabel" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2">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_lbl2" xlink:title="label: NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsIncMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl">Akcea Therapeutics, Inc. is a subsidiary of the Company and was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsIncMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl1">Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl1" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaTherapeuticsIncMember_lbl2" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl2">Akcea [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl2" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ShareBasedCompensationLineItems" xlink:label="ShareBasedCompensationLineItems" xlink:title="ShareBasedCompensationLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationLineItems_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationLineItems" xlink:to="ions_ShareBasedCompensationLineItems_lbl" xlink:title="label: ShareBasedCompensationLineItems to ions_ShareBasedCompensationLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationLineItems_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationLineItems_lbl1">Share-based Compensation [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationLineItems" xlink:to="ions_ShareBasedCompensationLineItems_lbl1" xlink:title="label: ShareBasedCompensationLineItems to ions_ShareBasedCompensationLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ShareBasedCompensationLineItems_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationLineItems_lbl2">Significant Accounting Policies [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationLineItems" xlink:to="ions_ShareBasedCompensationLineItems_lbl2" xlink:title="label: ShareBasedCompensationLineItems to ions_ShareBasedCompensationLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ShareBasedCompensationTable" xlink:label="ShareBasedCompensationTable" xlink:title="ShareBasedCompensationTable" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationTable_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationTable_lbl">Disclosure of information about share-based compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationTable" xlink:to="ions_ShareBasedCompensationTable_lbl" xlink:title="label: ShareBasedCompensationTable to ions_ShareBasedCompensationTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationTable_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationTable_lbl1">Share-based Compensation [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationTable" xlink:to="ions_ShareBasedCompensationTable_lbl1" xlink:title="label: ShareBasedCompensationTable to ions_ShareBasedCompensationTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:label="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:title="CashCashEquivalentsAndInvestmentsPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl" xml:lang="en-US" id="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl">Disclosure of accounting policy for cash, cash equivalents and investments.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:to="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl" xlink:title="label: CashCashEquivalentsAndInvestmentsPolicyTextBlock to ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl1" xml:lang="en-US" id="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl1">Cash, Cash Equivalents and Investments [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:to="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl1" xlink:title="label: CashCashEquivalentsAndInvestmentsPolicyTextBlock to ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl2" xml:lang="en-US" id="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl2">Cash, Cash Equivalents and Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:to="ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl2" xlink:title="label: CashCashEquivalentsAndInvestmentsPolicyTextBlock to ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LongTermObligationsNoncurrent" xlink:label="LongTermObligationsNoncurrent" xlink:title="LongTermObligationsNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsNoncurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl">Amount of long-term debt and lease obligation, classified as noncurrent.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsNoncurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl1">Long-term Obligations, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl1" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsNoncurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl2">Long-term obligations, less current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl2" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl2" />
  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>12
<FILENAME>ions-20190930_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 6.2.0.0 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://isispharm.com/role/SegmentInformationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SegmentInformationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsPfizerDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsNovartisDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsRocheDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsGskDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsBayerDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsBiogenDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/IncomeTaxesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#IncomeTaxesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2" xlink:type="simple" xlink:href="ions-20190930.xsd#OtherObligationsOperatingLeasesDetailsCalc2" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeasesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeasesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurementsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsInvestmentsTemporarilyImpairedDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsSummaryOfInvestmentsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesShareRepurchaseProgramDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesSegmentInformationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesLeasesDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesInventoryValuationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesCostOfProductsSoldDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesDeferredRevenueDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesContractsReceivableDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesRevenueRecognitionDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/BasisOfPresentationDetails" xlink:type="simple" xlink:href="ions-20190930.xsd#BasisOfPresentationDetails" />
  <link:roleRef roleURI="http://isispharm.com/role/SegmentInformationTables" xlink:type="simple" xlink:href="ions-20190930.xsd#SegmentInformationTables" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreementsTables" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeasesTables" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeasesTables" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurementsTables" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurementsTables" />
  <link:roleRef roleURI="http://isispharm.com/role/InvestmentsTables" xlink:type="simple" xlink:href="ions-20190930.xsd#InvestmentsTables" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesTables" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesTables" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPoliciesPolicies" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPoliciesPolicies" />
  <link:roleRef roleURI="http://isispharm.com/role/BasisOfPresentationPolicies" xlink:type="simple" xlink:href="ions-20190930.xsd#BasisOfPresentationPolicies" />
  <link:roleRef roleURI="http://isispharm.com/role/SegmentInformation" xlink:type="simple" xlink:href="ions-20190930.xsd#SegmentInformation" />
  <link:roleRef roleURI="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements" xlink:type="simple" xlink:href="ions-20190930.xsd#CollaborativeArrangementsAndLicensingAgreements" />
  <link:roleRef roleURI="http://isispharm.com/role/IncomeTaxes" xlink:type="simple" xlink:href="ions-20190930.xsd#IncomeTaxes" />
  <link:roleRef roleURI="http://isispharm.com/role/OperatingLeases" xlink:type="simple" xlink:href="ions-20190930.xsd#OperatingLeases" />
  <link:roleRef roleURI="http://isispharm.com/role/FairValueMeasurements" xlink:type="simple" xlink:href="ions-20190930.xsd#FairValueMeasurements" />
  <link:roleRef roleURI="http://isispharm.com/role/Investments" xlink:type="simple" xlink:href="ions-20190930.xsd#Investments" />
  <link:roleRef roleURI="http://isispharm.com/role/SignificantAccountingPolicies" xlink:type="simple" xlink:href="ions-20190930.xsd#SignificantAccountingPolicies" />
  <link:roleRef roleURI="http://isispharm.com/role/BasisOfPresentation" xlink:type="simple" xlink:href="ions-20190930.xsd#BasisOfPresentation" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfCashFlowsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfStockholdersEquityUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedStatementsOfOperationsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedBalanceSheetsUnauditedParenthetical" />
  <link:roleRef roleURI="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited" xlink:type="simple" xlink:href="ions-20190930.xsd#CondensedConsolidatedBalanceSheetsUnaudited" />
  <link:roleRef roleURI="http://isispharm.com/role/DocumentAndEntityInformation" xlink:type="simple" xlink:href="ions-20190930.xsd#DocumentAndEntityInformation" />
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/DocumentAndEntityInformation">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link: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="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link: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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link: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="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link: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="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link: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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link: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="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link: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="6.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link: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="7.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link: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="8.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link: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="9.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link: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="10.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link: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="11.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link: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="12.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link: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="13.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link: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="14.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentQuarterlyReport" xlink:label="DocumentQuarterlyReport" xlink:title="DocumentQuarterlyReport" />
    <link: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="15.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link: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="16.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link: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="17.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link: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="18.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link: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="19.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link: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="20.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link: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="21.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link: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="22.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link: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="23.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link: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="24.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link: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="25.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link: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="26.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link: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="27.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link: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="28.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsAbstract" xlink:label="AssetsAbstract" xlink:title="AssetsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetsCurrentAbstract" xlink:label="AssetsCurrentAbstract" xlink:title="AssetsCurrentAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:label="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:title="DeferredTaxAssetsLiabilitiesNetNoncurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsAbstract" xlink:to="DeferredTaxAssetsLiabilitiesNetNoncurrent" xlink:title="presentation: AssetsAbstract to DeferredTaxAssetsLiabilitiesNetNoncurrent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="StatementOfFinancialPositionAbstract" xlink:to="AssetsAbstract" xlink:title="presentation: StatementOfFinancialPositionAbstract to AssetsAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:label="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="LongTermDebtAndCapitalLeaseObligationsCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="LongTermDebtAndCapitalLeaseObligationsCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to LongTermDebtAndCapitalLeaseObligationsCurrent" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_LongTermObligationsNoncurrent" xlink:label="LongTermObligationsNoncurrent" xlink:title="LongTermObligationsNoncurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="LongTermObligationsNoncurrent" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to LongTermObligationsNoncurrent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterest" xlink:label="MinorityInterest" xlink:title="MinorityInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="MinorityInterest" xlink:title="presentation: StockholdersEquityAbstract to MinorityInterest" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StockholdersEquityAbstract" xlink:to="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="presentation: StockholdersEquityAbstract to StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" 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="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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StatementOfFinancialPositionAbstract" xlink:to="LiabilitiesAndStockholdersEquityAbstract" xlink:title="presentation: StatementOfFinancialPositionAbstract to LiabilitiesAndStockholdersEquityAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="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="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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementAbstract" xlink:label="IncomeStatementAbstract" xlink:title="IncomeStatementAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" 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="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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenuesAbstract" xlink:label="RevenuesAbstract" xlink:title="RevenuesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" xlink:title="presentation: StatementLineItems to IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="ProfitLoss" xlink:title="presentation: StatementLineItems to ProfitLoss" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAttributableToNoncontrollingInterest" xlink:label="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="NetIncomeLossAttributableToNoncontrollingInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="NetIncomeLossAttributableToNoncontrollingInterest" xlink:title="presentation: StatementLineItems to NetIncomeLossAttributableToNoncontrollingInterest" order="7.0" preferredLabel="http://www.xbrl.org/2009/role/negatedTerseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="8.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="11.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" 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://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="ProfitLoss" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to ProfitLoss" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:label="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:title="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:label="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:title="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ParentMember" xlink:label="ParentMember" xlink:title="ParentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="ParentMember" xlink:title="presentation: StatementEquityComponentsAxis to ParentMember" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NoncontrollingInterestMember" xlink:label="NoncontrollingInterestMember" xlink:title="NoncontrollingInterestMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="NoncontrollingInterestMember" xlink:title="presentation: StatementEquityComponentsAxis to NoncontrollingInterestMember" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" 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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues" xlink:label="StockIssuedDuringPeriodValueNewIssues" xlink:title="StockIssuedDuringPeriodValueNewIssues" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="StockIssuedDuringPeriodValueNewIssues" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to StockIssuedDuringPeriodValueNewIssues" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="StockIssuedDuringPeriodSharesNewIssues" xlink:title="StockIssuedDuringPeriodSharesNewIssues" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="StockIssuedDuringPeriodSharesNewIssues" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to StockIssuedDuringPeriodSharesNewIssues" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="8.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="11.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestPeriodIncreaseDecrease" xlink:label="MinorityInterestPeriodIncreaseDecrease" xlink:title="MinorityInterestPeriodIncreaseDecrease" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="MinorityInterestPeriodIncreaseDecrease" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to MinorityInterestPeriodIncreaseDecrease" order="12.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" preferredLabel="http://www.xbrl.org/2003/role/periodEndLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="14.0" 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://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NovartisInternationalAGMember" xlink:label="NovartisInternationalAGMember" xlink:title="NovartisInternationalAGMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NameOfMajorCustomerDomain" xlink:to="NovartisInternationalAGMember" xlink:title="presentation: NameOfMajorCustomerDomain to NovartisInternationalAGMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="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="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="StatementTable" xlink:to="MajorCustomersAxis" xlink:title="presentation: StatementTable to MajorCustomersAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="ProfitLoss" xlink:title="presentation: NetCashProvidedByUsedInOperatingActivitiesAbstract to ProfitLoss" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_OperatingLeaseRightOfUseAssetAmortization" xlink:label="OperatingLeaseRightOfUseAssetAmortization" xlink:title="OperatingLeaseRightOfUseAssetAmortization" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="OperatingLeaseRightOfUseAssetAmortization" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to OperatingLeaseRightOfUseAssetAmortization" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AmortizationOfDebtDiscountPremium" xlink:label="AmortizationOfDebtDiscountPremium" xlink:title="AmortizationOfDebtDiscountPremium" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="AmortizationOfDebtDiscountPremium" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to AmortizationOfDebtDiscountPremium" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AssetImpairmentCharges" xlink:label="AssetImpairmentCharges" xlink:title="AssetImpairmentCharges" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="AssetImpairmentCharges" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to AssetImpairmentCharges" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DeferredIncomeTaxExpenseBenefit" xlink:label="DeferredIncomeTaxExpenseBenefit" xlink:title="DeferredIncomeTaxExpenseBenefit" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="DeferredIncomeTaxExpenseBenefit" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to DeferredIncomeTaxExpenseBenefit" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:label="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="IncreaseDecreaseInAccruedAndDeferredLiabilities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInAccruedAndDeferredLiabilities" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInAccruedAndDeferredLiabilities" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="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/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StatementLineItems" xlink:to="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="presentation: StatementLineItems to NetCashProvidedByUsedInOperatingActivitiesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ions-20190930.xsd#ions_PaymentsToAcquireLicensesAndOtherAssets" xlink:label="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="PaymentsToAcquireLicensesAndOtherAssets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="PaymentsToAcquireLicensesAndOtherAssets" xlink:title="presentation: NetCashProvidedByUsedInInvestingActivitiesAbstract to PaymentsToAcquireLicensesAndOtherAssets" order="3.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StatementLineItems" xlink:to="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="presentation: StatementLineItems to NetCashProvidedByUsedInInvestingActivitiesAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInFinancingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="ProceedsFromIssuanceOfCommonStock" xlink:title="ProceedsFromIssuanceOfCommonStock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="ProceedsFromIssuanceOfCommonStock" xlink:title="presentation: NetCashProvidedByUsedInFinancingActivitiesAbstract to ProceedsFromIssuanceOfCommonStock" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:label="RepaymentsOfLongTermDebt" xlink:title="RepaymentsOfLongTermDebt" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="RepaymentsOfLongTermDebt" xlink:title="presentation: NetCashProvidedByUsedInFinancingActivitiesAbstract to RepaymentsOfLongTermDebt" order="3.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="presentation: StatementLineItems to NetCashProvidedByUsedInFinancingActivitiesAbstract" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:title="presentation: StatementLineItems to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StatementLineItems" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="presentation: StatementLineItems to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/periodStartLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StatementLineItems" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_2" xlink:title="presentation: StatementLineItems to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/periodEndLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SupplementalCashFlowInformationAbstract" xlink:label="SupplementalCashFlowInformationAbstract" xlink:title="SupplementalCashFlowInformationAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="StatementLineItems" xlink:to="SupplementalCashFlowInformationAbstract" xlink:title="presentation: StatementLineItems to SupplementalCashFlowInformationAbstract" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:label="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:label="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:to="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="presentation: CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract to RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CapitalExpendituresIncurredButNotYetPaid" xlink:label="CapitalExpendituresIncurredButNotYetPaid" xlink:title="CapitalExpendituresIncurredButNotYetPaid" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:to="CapitalExpendituresIncurredButNotYetPaid" xlink:title="presentation: CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract to CapitalExpendituresIncurredButNotYetPaid" 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="StatementLineItems" xlink:to="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="presentation: StatementLineItems to CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" 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="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="StatementOfCashFlowsAbstract" xlink:to="StatementTable" xlink:title="presentation: StatementOfCashFlowsAbstract to StatementTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/BasisOfPresentation">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/SignificantAccountingPolicies">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/Investments">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd#invest_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/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/FairValueMeasurements">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/OperatingLeases">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeasesAbstract" xlink:label="LeasesAbstract" xlink:title="LeasesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeasesTextBlock" xlink:label="LesseeOperatingLeasesTextBlock" xlink:title="LesseeOperatingLeasesTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LeasesAbstract" xlink:to="LesseeOperatingLeasesTextBlock" xlink:title="presentation: LeasesAbstract to LesseeOperatingLeasesTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/IncomeTaxes">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxDisclosureAbstract" xlink:label="IncomeTaxDisclosureAbstract" xlink:title="IncomeTaxDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/SegmentInformation">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingAbstract" xlink:label="SegmentReportingAbstract" xlink:title="SegmentReportingAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureTextBlock" xlink:label="SegmentReportingDisclosureTextBlock" xlink:title="SegmentReportingDisclosureTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentReportingAbstract" xlink:to="SegmentReportingDisclosureTextBlock" xlink:title="presentation: SegmentReportingAbstract to SegmentReportingDisclosureTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/BasisOfPresentationPolicies">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/SignificantAccountingPoliciesPolicies">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:label="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:title="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" xlink:title="presentation: AccountingPoliciesAbstract to ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:label="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:title="CashCashEquivalentsAndInvestmentsPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="CashCashEquivalentsAndInvestmentsPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to CashCashEquivalentsAndInvestmentsPolicyTextBlock" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="11.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="12.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="13.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="14.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="15.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/SignificantAccountingPoliciesTables">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:label="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:title="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:label="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:title="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ShareBasedCompensationTable" xlink:label="ShareBasedCompensationTable" xlink:title="ShareBasedCompensationTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" 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="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="presentation: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" 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="ShareBasedCompensationTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="presentation: ShareBasedCompensationTable to ConsolidatedEntitiesAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ShareBasedCompensationLineItems" xlink:label="ShareBasedCompensationLineItems" xlink:title="ShareBasedCompensationLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ShareBasedCompensationLineItems" xlink:to="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="presentation: ShareBasedCompensationLineItems to ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ShareBasedCompensationLineItems" xlink:to="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="presentation: ShareBasedCompensationLineItems to ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" 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="ShareBasedCompensationTable" xlink:to="ShareBasedCompensationLineItems" xlink:title="presentation: ShareBasedCompensationTable to ShareBasedCompensationLineItems" 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="AccountingPoliciesAbstract" xlink:to="ShareBasedCompensationTable" xlink:title="presentation: AccountingPoliciesAbstract to ShareBasedCompensationTable" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/InvestmentsTables">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/FairValueMeasurementsTables">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/OperatingLeasesTables">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeasesAbstract" xlink:label="LeasesAbstract" xlink:title="LeasesAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseInformationTableTextBlock" xlink:label="LesseeOperatingLeaseInformationTableTextBlock" xlink:title="LesseeOperatingLeaseInformationTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LeasesAbstract" xlink:to="LesseeOperatingLeaseInformationTableTextBlock" xlink:title="presentation: LeasesAbstract to LesseeOperatingLeaseInformationTableTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:label="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:title="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LeasesAbstract" xlink:to="ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" xlink:title="presentation: LeasesAbstract to ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsBiogenMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsRocheMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" 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="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="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="TypeOfArrangementAxis" xlink:title="presentation: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to TypeOfArrangementAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:title="presentation: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" 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="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="presentation: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" 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="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsAbstract to CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SegmentInformationTables">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingAbstract" xlink:label="SegmentReportingAbstract" xlink:title="SegmentReportingAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:label="ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:title="ScheduleOfSegmentReportingInformationBySegmentTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentReportingAbstract" xlink:to="ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:title="presentation: SegmentReportingAbstract to ScheduleOfSegmentReportingInformationBySegmentTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/BasisOfPresentationDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: OwnershipDomain to AkceaTherapeuticsIncMember" 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="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="presentation: OwnershipAxis to OwnershipDomain" 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="MinorityInterestTable" xlink:to="OwnershipAxis" xlink:title="presentation: MinorityInterestTable to OwnershipAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScenarioUnspecifiedDomain" xlink:to="ScenarioForecastMember" xlink:title="presentation: ScenarioUnspecifiedDomain to ScenarioForecastMember" 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="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain" xlink:title="presentation: StatementScenarioAxis to ScenarioUnspecifiedDomain" 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="MinorityInterestTable" xlink:to="StatementScenarioAxis" xlink:title="presentation: MinorityInterestTable to StatementScenarioAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:label="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:title="ProceedsFromIssuanceOrSaleOfEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:to="MinorityInterestOwnershipPercentageByParent" xlink:title="presentation: ProceedsFromIssuanceOrSaleOfEquityAbstract to MinorityInterestOwnershipPercentageByParent" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="presentation: ProceedsFromIssuanceOrSaleOfEquityAbstract to ReceiptOfSharesInSubsidiary" 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="MinorityInterestLineItems" xlink:to="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:title="presentation: MinorityInterestLineItems to ProceedsFromIssuanceOrSaleOfEquityAbstract" 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="MinorityInterestTable" xlink:to="MinorityInterestLineItems" xlink:title="presentation: MinorityInterestTable to MinorityInterestLineItems" 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="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:to="MinorityInterestTable" xlink:title="presentation: OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract to MinorityInterestTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBayerMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsBayerMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:to="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsBayerMember to CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" 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="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsBayerMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsBayerMember" 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="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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISLRRK2Member" xlink:label="IONISLRRK2Member" xlink:title="IONISLRRK2Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="IONISLRRK2Member" xlink:title="presentation: ProductsAndServicesDomain to IONISLRRK2Member" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="ProductsAndServicesDomain" xlink:to="LicensingAndOtherRoyaltiesMember" xlink:title="presentation: ProductsAndServicesDomain to LicensingAndOtherRoyaltiesMember" 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="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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:label="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="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="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://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractReceivablesAbstract" xlink:label="ContractReceivablesAbstract" xlink:title="ContractReceivablesAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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: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://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CostOfGoodsAndServicesSoldAbstract" xlink:label="CostOfGoodsAndServicesSoldAbstract" xlink:title="CostOfGoodsAndServicesSoldAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CostOfProductsSoldPreviouslyRecognized" xlink:label="CostOfProductsSoldPreviouslyRecognized" xlink:title="CostOfProductsSoldPreviouslyRecognized" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CostOfGoodsAndServicesSoldAbstract" xlink:to="CostOfProductsSoldPreviouslyRecognized" xlink:title="presentation: CostOfGoodsAndServicesSoldAbstract to CostOfProductsSoldPreviouslyRecognized" 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="CostOfGoodsAndServicesSoldAbstract" xlink:title="presentation: AccountingPoliciesAbstract to CostOfGoodsAndServicesSoldAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: OwnershipDomain to AkceaTherapeuticsIncMember" 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="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="presentation: OwnershipAxis to OwnershipDomain" 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="MinorityInterestTable" xlink:to="OwnershipAxis" xlink:title="presentation: MinorityInterestTable to OwnershipAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScenarioUnspecifiedDomain" xlink:to="ScenarioForecastMember" xlink:title="presentation: ScenarioUnspecifiedDomain to ScenarioForecastMember" 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="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain" xlink:title="presentation: StatementScenarioAxis to ScenarioUnspecifiedDomain" 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="MinorityInterestTable" xlink:to="StatementScenarioAxis" xlink:title="presentation: MinorityInterestTable to StatementScenarioAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NoncontrollingInterestAbstract" xlink:label="NoncontrollingInterestAbstract" xlink:title="NoncontrollingInterestAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NoncontrollingInterestAbstract" xlink:to="MinorityInterestOwnershipPercentageByParent" xlink:title="presentation: NoncontrollingInterestAbstract to MinorityInterestOwnershipPercentageByParent" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NoncontrollingInterestAbstract" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="presentation: NoncontrollingInterestAbstract to ReceiptOfSharesInSubsidiary" 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="MinorityInterestLineItems" xlink:to="NoncontrollingInterestAbstract" xlink:title="presentation: MinorityInterestLineItems to NoncontrollingInterestAbstract" 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="MinorityInterestTable" xlink:to="MinorityInterestLineItems" xlink:title="presentation: MinorityInterestTable to MinorityInterestLineItems" 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="AccountingPoliciesAbstract" xlink:to="MinorityInterestTable" xlink:title="presentation: AccountingPoliciesAbstract to MinorityInterestTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:label="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="CashCashEquivalentsAndShortTermInvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="presentation: AccountingPoliciesAbstract to CashCashEquivalentsAndShortTermInvestmentsAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:label="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:title="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InventoryWriteDown" xlink:label="InventoryWriteDown" xlink:title="InventoryWriteDown" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:to="InventoryWriteDown" xlink:title="presentation: InventoryRawMaterialsAndSuppliesNetOfReservesAbstract to InventoryWriteDown" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:to="InventoryNet" xlink:title="presentation: InventoryRawMaterialsAndSuppliesNetOfReservesAbstract to InventoryNet" 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="AccountingPoliciesAbstract" xlink:to="InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" xlink:title="presentation: AccountingPoliciesAbstract to InventoryRawMaterialsAndSuppliesNetOfReservesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:label="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:title="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="AdjustmentsForNewAccountingPronouncementsAxis" xlink:title="AdjustmentsForNewAccountingPronouncementsAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="TypeOfAdoptionMember" xlink:title="TypeOfAdoptionMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingStandardsUpdate201602Member" xlink:label="AccountingStandardsUpdate201602Member" xlink:title="AccountingStandardsUpdate201602Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TypeOfAdoptionMember" xlink:to="AccountingStandardsUpdate201602Member" xlink:title="presentation: TypeOfAdoptionMember to AccountingStandardsUpdate201602Member" 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="AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="TypeOfAdoptionMember" xlink:title="presentation: AdjustmentsForNewAccountingPronouncementsAxis to TypeOfAdoptionMember" 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="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="AdjustmentsForNewAccountingPronouncementsAxis" xlink:title="presentation: NewAccountingPronouncementsOrChangeInAccountingPrincipleTable to AdjustmentsForNewAccountingPronouncementsAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:label="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:title="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseRightOfUseAsset" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseRightOfUseAsset" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseLiability" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseLiability" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseLiabilityCurrent" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseLiabilityCurrent" 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="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="LesseeDisclosureAbstract" xlink:title="presentation: NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems 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="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:title="presentation: NewAccountingPronouncementsOrChangeInAccountingPrincipleTable to NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" 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="NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:title="presentation: AccountingPoliciesAbstract to NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:label="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:title="ScheduleOfEarningsPerShareBasicByCommonClassTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: OwnershipDomain to AkceaTherapeuticsIncMember" 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="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="presentation: OwnershipAxis to OwnershipDomain" 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="OwnershipAxis" xlink:title="presentation: ScheduleOfEarningsPerShareBasicByCommonClassTable to OwnershipAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="StatementClassOfStockAxis" xlink:title="StatementClassOfStockAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ClassOfStockDomain" xlink:label="ClassOfStockDomain" xlink:title="ClassOfStockDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConvertiblePreferredStockMember" xlink:label="ConvertiblePreferredStockMember" xlink:title="ConvertiblePreferredStockMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ClassOfStockDomain" xlink:to="ConvertiblePreferredStockMember" xlink:title="presentation: ClassOfStockDomain to ConvertiblePreferredStockMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="ClassOfStockDomain" xlink:to="CommonStockMember" xlink:title="presentation: ClassOfStockDomain to CommonStockMember" 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="StatementClassOfStockAxis" xlink:to="ClassOfStockDomain" xlink:title="presentation: StatementClassOfStockAxis to ClassOfStockDomain" 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="StatementClassOfStockAxis" xlink:title="presentation: ScheduleOfEarningsPerShareBasicByCommonClassTable to StatementClassOfStockAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain" xlink:title="SegmentDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentDomain" xlink:to="IonisCoreMember" xlink:title="presentation: SegmentDomain to IonisCoreMember" 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="StatementBusinessSegmentsAxis" xlink:to="SegmentDomain" xlink:title="presentation: StatementBusinessSegmentsAxis to SegmentDomain" 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="StatementBusinessSegmentsAxis" xlink:title="presentation: ScheduleOfEarningsPerShareBasicByCommonClassTable to StatementBusinessSegmentsAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="AwardTypeAxis" xlink:title="AwardTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <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/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="RestrictedStockMember" xlink:title="RestrictedStockMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="RestrictedStockMember" xlink:title="presentation: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to RestrictedStockMember" 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="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="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="AwardTypeAxis" xlink:title="presentation: ScheduleOfEarningsPerShareBasicByCommonClassTable to AwardTypeAxis" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="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="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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EarningsPerShareBasicLineItems" xlink:label="EarningsPerShareBasicLineItems" xlink:title="EarningsPerShareBasicLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EarningsPerShareBasicAbstract" xlink:label="EarningsPerShareBasicAbstract" xlink:title="EarningsPerShareBasicAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:label="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="WeightedAverageNumberOfSharesOwnedInSubsidiary" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="presentation: EarningsPerShareBasicAbstract to WeightedAverageNumberOfSharesOwnedInSubsidiary" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicAbstract" xlink:to="NetIncomeLoss" xlink:title="presentation: EarningsPerShareBasicAbstract to NetIncomeLoss" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic" xlink:label="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:title="NetIncomeLossAvailableToCommonStockholdersBasic" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:title="presentation: EarningsPerShareBasicAbstract to NetIncomeLossAvailableToCommonStockholdersBasic" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicAbstract" xlink:to="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="presentation: EarningsPerShareBasicAbstract to WeightedAverageNumberOfSharesOutstandingBasic" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:label="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:title="NetIncomeLossAvailableToCommonStockholdersDiluted" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="NetIncomeLossAvailableToCommonStockholdersDiluted" xlink:title="presentation: EarningsPerShareBasicAbstract to NetIncomeLossAvailableToCommonStockholdersDiluted" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="presentation: EarningsPerShareBasicAbstract to IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="presentation: EarningsPerShareBasicAbstract to IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicAbstract" xlink:to="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="presentation: EarningsPerShareBasicAbstract to WeightedAverageNumberOfDilutedSharesOutstanding" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EarningsPerShareBasicAbstract" xlink:to="EarningsPerShareDiluted" xlink:title="presentation: EarningsPerShareBasicAbstract to EarningsPerShareDiluted" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" 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="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="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://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" 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="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="presentation: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" 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="ConsolidatedEntitiesAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to ConsolidatedEntitiesAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameAxis" xlink:label="PlanNameAxis" xlink:title="PlanNameAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PlanNameDomain" xlink:label="PlanNameDomain" xlink:title="PlanNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_EquityIncentivePlan2011Member" xlink:label="EquityIncentivePlan2011Member" xlink:title="EquityIncentivePlan2011Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PlanNameDomain" xlink:to="EquityIncentivePlan2011Member" xlink:title="presentation: PlanNameDomain to EquityIncentivePlan2011Member" 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="PlanNameAxis" xlink:to="PlanNameDomain" xlink:title="presentation: PlanNameAxis to PlanNameDomain" 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="PlanNameAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to PlanNameAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="AwardTypeAxis" xlink:title="AwardTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <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="ions-20190930.xsd#ions_BoardOfDirectorStockOptionMember" xlink:label="BoardOfDirectorStockOptionMember" xlink:title="BoardOfDirectorStockOptionMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="BoardOfDirectorStockOptionMember" xlink:title="presentation: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to BoardOfDirectorStockOptionMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" 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="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="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis" xlink:label="RelatedPartyTransactionsByRelatedPartyAxis" xlink:title="RelatedPartyTransactionsByRelatedPartyAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_RelatedPartyDomain" xlink:label="RelatedPartyDomain" xlink:title="RelatedPartyDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_EmployeeMember" xlink:label="EmployeeMember" xlink:title="EmployeeMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RelatedPartyDomain" xlink:to="EmployeeMember" xlink:title="presentation: RelatedPartyDomain to EmployeeMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_BoardOfDirectorsMember" xlink:label="BoardOfDirectorsMember" xlink:title="BoardOfDirectorsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RelatedPartyDomain" xlink:to="BoardOfDirectorsMember" xlink:title="presentation: RelatedPartyDomain to BoardOfDirectorsMember" 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="RelatedPartyTransactionsByRelatedPartyAxis" xlink:to="RelatedPartyDomain" xlink:title="presentation: RelatedPartyTransactionsByRelatedPartyAxis to RelatedPartyDomain" 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="RelatedPartyTransactionsByRelatedPartyAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to RelatedPartyTransactionsByRelatedPartyAxis" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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: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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:label="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:title="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="presentation: DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="presentation: DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" 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="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:label="CommonStockCapitalSharesReservedForFutureIssuance" xlink:title="CommonStockCapitalSharesReservedForFutureIssuance" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="CommonStockCapitalSharesReservedForFutureIssuance" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to CommonStockCapitalSharesReservedForFutureIssuance" 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="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" 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="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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="ConsolidatedEntitiesAxis" xlink:title="presentation: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to ConsolidatedEntitiesAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="IncomeStatementLocationAxis" xlink:title="IncomeStatementLocationAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="IncomeStatementLocationDomain" xlink:title="IncomeStatementLocationDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeStatementLocationDomain" xlink:to="ResearchDevelopmentAndPatentMember" xlink:title="presentation: IncomeStatementLocationDomain to ResearchDevelopmentAndPatentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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/terseLabel" />
    <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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfExecutiveOfficersTerminatingEmployment" xlink:label="NumberOfExecutiveOfficersTerminatingEmployment" xlink:title="NumberOfExecutiveOfficersTerminatingEmployment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationAbstract" xlink:to="NumberOfExecutiveOfficersTerminatingEmployment" xlink:title="presentation: ShareBasedCompensationAbstract to NumberOfExecutiveOfficersTerminatingEmployment" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="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="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="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://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockRepurchaseProgramAuthorizedAmount1" xlink:label="StockRepurchaseProgramAuthorizedAmount1" xlink:title="StockRepurchaseProgramAuthorizedAmount1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="StockRepurchaseProgramAuthorizedAmount1" xlink:title="presentation: AccountingPoliciesAbstract to StockRepurchaseProgramAuthorizedAmount1" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StockRepurchasedDuringPeriodShares" xlink:label="StockRepurchasedDuringPeriodShares" xlink:title="StockRepurchasedDuringPeriodShares" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="StockRepurchasedDuringPeriodShares" xlink:title="presentation: AccountingPoliciesAbstract to StockRepurchasedDuringPeriodShares" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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-20190930.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-20190930.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:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd#invest_InvestmentsScheduleAbstract" xlink:label="InvestmentsScheduleAbstract" xlink:title="InvestmentsScheduleAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="InvestmentsScheduleAbstract" xlink:to="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="presentation: InvestmentsScheduleAbstract to NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="InvestmentsScheduleAbstract" xlink:to="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="presentation: InvestmentsScheduleAbstract to NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" 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="InvestmentsAbstract" xlink:to="InvestmentsScheduleAbstract" xlink:title="presentation: InvestmentsAbstract to InvestmentsScheduleAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="InvestmentTypeAxis" xlink:title="InvestmentTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember" xlink:title="InvestmentTypeCategorizationMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="InvestmentTypeCategorizationMember" xlink:to="DebtSecuritiesMember" xlink:title="presentation: InvestmentTypeCategorizationMember 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="InvestmentTypeAxis" xlink:to="InvestmentTypeCategorizationMember" xlink:title="presentation: InvestmentTypeAxis to InvestmentTypeCategorizationMember" 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="InvestmentTypeAxis" xlink:title="presentation: InvestmentHoldingsTable to InvestmentTypeAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentSecondaryCategorizationAxis" xlink:label="InvestmentSecondaryCategorizationAxis" xlink:title="InvestmentSecondaryCategorizationAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentsBySecondaryCategorizationDomain" xlink:label="InvestmentsBySecondaryCategorizationDomain" xlink:title="InvestmentsBySecondaryCategorizationDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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-20190930.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-20190930.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: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="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="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://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeAxis" xlink:label="InvestmentTypeAxis" xlink:title="InvestmentTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentTypeCategorizationMember" xlink:label="InvestmentTypeCategorizationMember" xlink:title="InvestmentTypeCategorizationMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentTypeCategorizationMember" xlink:to="DebtSecuritiesMember" xlink:title="presentation: InvestmentTypeCategorizationMember 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="InvestmentTypeAxis" xlink:to="InvestmentTypeCategorizationMember" xlink:title="presentation: InvestmentTypeAxis to InvestmentTypeCategorizationMember" 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="InvestmentTypeAxis" xlink:title="presentation: InvestmentHoldingsTable to InvestmentTypeAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAbstract" xlink:label="AvailableForSaleSecuritiesAbstract" xlink:title="AvailableForSaleSecuritiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:label="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:title="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" order="2.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" order="4.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss" order="6.0" 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="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://isispharm.com/role/FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="FairValueByMeasurementFrequencyAxis" xlink:title="FairValueByMeasurementFrequencyAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="FairValueMeasurementFrequencyDomain" xlink:title="FairValueMeasurementFrequencyDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="FairValueByFairValueHierarchyLevelAxis" xlink:title="FairValueByFairValueHierarchyLevelAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="FairValueMeasurementsFairValueHierarchyDomain" xlink:title="FairValueMeasurementsFairValueHierarchyDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="BalanceSheetLocationAxis" xlink:title="BalanceSheetLocationAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="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="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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_AvailableForSaleSecurities" xlink:label="AvailableForSaleSecurities" xlink:title="AvailableForSaleSecurities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="AvailableForSaleSecurities" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to AvailableForSaleSecurities" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="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://isispharm.com/role/OperatingLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LeasesAbstract" xlink:label="LeasesAbstract" xlink:title="LeasesAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" 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="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="presentation: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" 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="ConsolidatedEntitiesAxis" xlink:title="presentation: LesseeLeaseDescriptionTable to ConsolidatedEntitiesAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="PropertyPlantAndEquipmentByTypeAxis" xlink:title="PropertyPlantAndEquipmentByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="PropertyPlantAndEquipmentTypeDomain" xlink:title="PropertyPlantAndEquipmentTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:label="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:title="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" xlink:title="presentation: PropertyPlantAndEquipmentTypeDomain to OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:label="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:title="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" xlink:title="presentation: PropertyPlantAndEquipmentTypeDomain to OfficeSpaceSubleasedToAkceaTherapeuticsIncMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_OfficeSpaceForCorporateHeadquartersMember" xlink:label="OfficeSpaceForCorporateHeadquartersMember" xlink:title="OfficeSpaceForCorporateHeadquartersMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="OfficeSpaceForCorporateHeadquartersMember" xlink:title="presentation: PropertyPlantAndEquipmentTypeDomain to OfficeSpaceForCorporateHeadquartersMember" 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="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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:label="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" xlink:title="presentation: LesseeDisclosureAbstract to LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="LesseeOperatingLeaseRenewalTerm" xlink:title="LesseeOperatingLeaseRenewalTerm" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseRenewalTerm" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseRenewalTerm" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseTermOfContract" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseTermOfContract" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:label="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="LesseeOperatingLeasePeriodOfFreeRent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeasePeriodOfFreeRent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:label="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="LesseeOperatingLeaseAllowanceForTenantImprovements" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseAllowanceForTenantImprovements" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseAllowanceForTenantImprovements" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:label="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:label="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseRightOfUseAsset" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseRightOfUseAsset" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseLiability" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseLiability" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:label="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="OperatingLeaseWeightedAverageRemainingLeaseTerm1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseWeightedAverageRemainingLeaseTerm1" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseWeightedAverageRemainingLeaseTerm1" order="10.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent" xlink:label="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="OperatingLeaseWeightedAverageDiscountRatePercent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseWeightedAverageDiscountRatePercent" order="11.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseLiabilityCurrent" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseLiabilityCurrent" order="12.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeasePayments" xlink:label="OperatingLeasePayments" xlink:title="OperatingLeasePayments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeasePayments" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeasePayments" order="13.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:label="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="OperatingLeaseLiabilitiesPaymentsDueAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDueYearThree" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDueYearFour" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDueYearFive" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityPaymentsDue" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" order="7.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="OperatingLeaseLiability" xlink:title="presentation: OperatingLeaseLiabilitiesPaymentsDueAbstract to OperatingLeaseLiability" 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="LesseeDisclosureAbstract" xlink:to="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseLiabilitiesPaymentsDueAbstract" order="14.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingLeaseExpense" xlink:label="OperatingLeaseExpense" xlink:title="OperatingLeaseExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="OperatingLeaseExpense" xlink:title="presentation: LesseeDisclosureAbstract to OperatingLeaseExpense" order="15.0" 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="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="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="LeasesAbstract" xlink:to="LesseeLeaseDescriptionTable" xlink:title="presentation: LeasesAbstract to LesseeLeaseDescriptionTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2" />
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/IncomeTaxesDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IncomeTaxDisclosureAbstract" xlink:label="IncomeTaxDisclosureAbstract" xlink:title="IncomeTaxDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:label="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:title="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:to="IncomeTaxExpenseBenefit" xlink:title="presentation: EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract to IncomeTaxExpenseBenefit" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperations" xlink:label="EffectiveIncomeTaxRateContinuingOperations" xlink:title="EffectiveIncomeTaxRateContinuingOperations" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:to="EffectiveIncomeTaxRateContinuingOperations" xlink:title="presentation: EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract to EffectiveIncomeTaxRateContinuingOperations" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:label="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:title="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:to="EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" xlink:title="presentation: EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract to EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" 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="IncomeTaxDisclosureAbstract" xlink:to="EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" xlink:title="presentation: IncomeTaxDisclosureAbstract to EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsBiogenMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember" 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="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsBiogenMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsBiogenMember" 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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentServicesMember" xlink:label="ResearchAndDevelopmentServicesMember" xlink:title="ResearchAndDevelopmentServicesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentServicesMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentServicesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISMAPTMember" xlink:label="IONISMAPTMember" xlink:title="IONISMAPTMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="IONISMAPTMember" xlink:title="presentation: ProductsAndServicesDomain to IONISMAPTMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IONISLRRK2Member" xlink:label="IONISLRRK2Member" xlink:title="IONISLRRK2Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="IONISLRRK2Member" xlink:title="presentation: ProductsAndServicesDomain to IONISLRRK2Member" 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="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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:label="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:title="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:label="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="UpfrontPaymentReceivedIncludingPurchaseOfStock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to UpfrontPaymentReceivedIncludingPurchaseOfStock" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfMilestonePaymentsAchieved" xlink:label="NumberOfMilestonePaymentsAchieved" xlink:title="NumberOfMilestonePaymentsAchieved" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NumberOfMilestonePaymentsAchieved" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NumberOfMilestonePaymentsAchieved" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MilestonePaymentsReceived" xlink:label="MilestonePaymentsReceived" xlink:title="MilestonePaymentsReceived" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="MilestonePaymentsReceived" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to MilestonePaymentsReceived" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfNewTargetsAdvanced" xlink:label="NumberOfNewTargetsAdvanced" xlink:title="NumberOfNewTargetsAdvanced" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NumberOfNewTargetsAdvanced" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NumberOfNewTargetsAdvanced" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:label="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="PaymentsIncludedInTransactionPriceForPerformanceObligation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="PaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to PaymentsIncludedInTransactionPriceForPerformanceObligation" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NextPotentialMilestonePayment" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NextPotentialMilestonePayment" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="10.0" 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="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="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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" 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/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="SubsequentEventMember" xlink:title="SubsequentEventMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SubsequentEventTypeDomain" xlink:to="SubsequentEventMember" xlink:title="presentation: SubsequentEventTypeDomain to SubsequentEventMember" 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="SubsequentEventTypeAxis" xlink:to="SubsequentEventTypeDomain" xlink:title="presentation: SubsequentEventTypeAxis to SubsequentEventTypeDomain" 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="SubsequentEventTypeAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to SubsequentEventTypeAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MilestonePaymentEarned" xlink:label="MilestonePaymentEarned" xlink:title="MilestonePaymentEarned" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="MilestonePaymentEarned" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to MilestonePaymentEarned" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NextPotentialMilestonePayment" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NextPotentialMilestonePayment" 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="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="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="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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember" 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/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_LicenseMember" xlink:label="LicenseMember" xlink:title="LicenseMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="LicenseMember" xlink:title="presentation: ProductsAndServicesDomain to LicenseMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" 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="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ProductOrServiceAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ProductOrServiceAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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: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="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfDrugsCurrentlyBeingAdvanced" xlink:label="NumberOfDrugsCurrentlyBeingAdvanced" xlink:title="NumberOfDrugsCurrentlyBeingAdvanced" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NumberOfDrugsCurrentlyBeingAdvanced" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NumberOfDrugsCurrentlyBeingAdvanced" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NextPotentialMilestonePayment" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NextPotentialMilestonePayment" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:label="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="CollaborativeArrangementsAndLicensingAgreementsRocheMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsRocheMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsRocheMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" 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="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementsAndLicensingAgreementsRocheMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementsAndLicensingAgreementsRocheMember" 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/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisHttMember" xlink:label="IonisHttMember" xlink:title="IonisHttMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="IonisHttMember" xlink:title="presentation: ProductsAndServicesDomain to IonisHttMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" 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="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ProductOrServiceAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ProductOrServiceAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NumberOfCollaborationAgreements" xlink:label="NumberOfCollaborationAgreements" xlink:title="NumberOfCollaborationAgreements" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NumberOfCollaborationAgreements" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NumberOfCollaborationAgreements" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_NextPotentialMilestonePayment" xlink:label="NextPotentialMilestonePayment" xlink:title="NextPotentialMilestonePayment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NextPotentialMilestonePayment" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NextPotentialMilestonePayment" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="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="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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" 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="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="presentation: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" 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="ConsolidatedEntitiesAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConsolidatedEntitiesAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember" 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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AKCEAAPOALMember" xlink:label="AKCEAAPOALMember" xlink:title="AKCEAAPOALMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="AKCEAAPOALMember" xlink:title="presentation: ProductsAndServicesDomain to AKCEAAPOALMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" 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="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="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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: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="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_SublicenseFeePaidForLicenseOfDrug" xlink:label="SublicenseFeePaidForLicenseOfDrug" xlink:title="SublicenseFeePaidForLicenseOfDrug" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="SublicenseFeePaidForLicenseOfDrug" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to SublicenseFeePaidForLicenseOfDrug" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to ReceiptOfSharesInSubsidiary" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="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="6.0" 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://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidatedEntitiesDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: ConsolidatedEntitiesDomain to AkceaTherapeuticsIncMember" 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="ConsolidatedEntitiesAxis" xlink:to="ConsolidatedEntitiesDomain" xlink:title="presentation: ConsolidatedEntitiesAxis to ConsolidatedEntitiesDomain" 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="ConsolidatedEntitiesAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConsolidatedEntitiesAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:label="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:title="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember" 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="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.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: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="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="SubsequentEventTypeDomain" xlink:title="SubsequentEventTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="SubsequentEventMember" xlink:title="SubsequentEventMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SubsequentEventTypeDomain" xlink:to="SubsequentEventMember" xlink:title="presentation: SubsequentEventTypeDomain to SubsequentEventMember" 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="SubsequentEventTypeAxis" xlink:to="SubsequentEventTypeDomain" xlink:title="presentation: SubsequentEventTypeAxis to SubsequentEventTypeDomain" 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="SubsequentEventTypeAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to SubsequentEventTypeAxis" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScenarioUnspecifiedDomain" xlink:to="ScenarioForecastMember" xlink:title="presentation: ScenarioUnspecifiedDomain to ScenarioForecastMember" 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="StatementScenarioAxis" xlink:to="ScenarioUnspecifiedDomain" xlink:title="presentation: StatementScenarioAxis to ScenarioUnspecifiedDomain" 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="StatementScenarioAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to StatementScenarioAxis" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_UpfrontLicenseFeeToBeReceived" xlink:label="UpfrontLicenseFeeToBeReceived" xlink:title="UpfrontLicenseFeeToBeReceived" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="UpfrontLicenseFeeToBeReceived" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to UpfrontLicenseFeeToBeReceived" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfDrug" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="RoyaltyPercentageReceivedOnNetSalesOfDrug" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to RoyaltyPercentageReceivedOnNetSalesOfDrug" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_SublicenseFeePaidForLicenseOfDrug" xlink:label="SublicenseFeePaidForLicenseOfDrug" xlink:title="SublicenseFeePaidForLicenseOfDrug" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="SublicenseFeePaidForLicenseOfDrug" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to SublicenseFeePaidForLicenseOfDrug" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_ReceiptOfSharesInSubsidiary" xlink:label="ReceiptOfSharesInSubsidiary" xlink:title="ReceiptOfSharesInSubsidiary" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ReceiptOfSharesInSubsidiary" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to ReceiptOfSharesInSubsidiary" order="4.0" 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="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://isispharm.com/role/SegmentInformationDetails">
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingAbstract" xlink:label="SegmentReportingAbstract" xlink:title="SegmentReportingAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_NumberOfReportableSegments" xlink:label="NumberOfReportableSegments" xlink:title="NumberOfReportableSegments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentReportingAbstract" xlink:to="NumberOfReportableSegments" xlink:title="presentation: SegmentReportingAbstract to NumberOfReportableSegments" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OwnershipDomain" xlink:to="AkceaTherapeuticsIncMember" xlink:title="presentation: OwnershipDomain to AkceaTherapeuticsIncMember" 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="OwnershipAxis" xlink:to="OwnershipDomain" xlink:title="presentation: OwnershipAxis to OwnershipDomain" 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="MinorityInterestTable" xlink:to="OwnershipAxis" xlink:title="presentation: MinorityInterestTable to OwnershipAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:to="MinorityInterestOwnershipPercentageByParent" xlink:title="presentation: SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract to MinorityInterestOwnershipPercentageByParent" 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="MinorityInterestLineItems" xlink:to="SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" xlink:title="presentation: MinorityInterestLineItems to SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract" 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="MinorityInterestTable" xlink:to="MinorityInterestLineItems" xlink:title="presentation: MinorityInterestTable to MinorityInterestLineItems" 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="SegmentReportingAbstract" xlink:to="MinorityInterestTable" xlink:title="presentation: SegmentReportingAbstract to MinorityInterestTable" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable" xlink:label="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:title="ScheduleOfSegmentReportingInformationBySegmentTable" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsAxis" xlink:label="ConsolidationItemsAxis" xlink:title="ConsolidationItemsAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ConsolidationItemsDomain" xlink:label="ConsolidationItemsDomain" xlink:title="ConsolidationItemsDomain" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_OperatingSegmentsMember" xlink:label="OperatingSegmentsMember" xlink:title="OperatingSegmentsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidationItemsDomain" xlink:to="OperatingSegmentsMember" xlink:title="presentation: ConsolidationItemsDomain to OperatingSegmentsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_IntersegmentEliminationMember" xlink:label="IntersegmentEliminationMember" xlink:title="IntersegmentEliminationMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConsolidationItemsDomain" xlink:to="IntersegmentEliminationMember" xlink:title="presentation: ConsolidationItemsDomain to IntersegmentEliminationMember" 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="ConsolidationItemsAxis" xlink:to="ConsolidationItemsDomain" xlink:title="presentation: ConsolidationItemsAxis to ConsolidationItemsDomain" 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="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="ConsolidationItemsAxis" xlink:title="presentation: ScheduleOfSegmentReportingInformationBySegmentTable to ConsolidationItemsAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentDomain" xlink:label="SegmentDomain" xlink:title="SegmentDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentDomain" xlink:to="IonisCoreMember" xlink:title="presentation: SegmentDomain to IonisCoreMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_AkceaTherapeuticsMember" xlink:label="AkceaTherapeuticsMember" xlink:title="AkceaTherapeuticsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentDomain" xlink:to="AkceaTherapeuticsMember" xlink:title="presentation: SegmentDomain to AkceaTherapeuticsMember" 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="StatementBusinessSegmentsAxis" xlink:to="SegmentDomain" xlink:title="presentation: StatementBusinessSegmentsAxis to SegmentDomain" 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="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="StatementBusinessSegmentsAxis" xlink:title="presentation: ScheduleOfSegmentReportingInformationBySegmentTable to StatementBusinessSegmentsAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20190930.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="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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-20190930.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/terseLabel" />
    <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-20190930.xsd#ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:label="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember" 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="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="ProductOrServiceAxis" xlink:title="presentation: ScheduleOfSegmentReportingInformationBySegmentTable to ProductOrServiceAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingInformationLineItems" xlink:label="SegmentReportingInformationLineItems" xlink:title="SegmentReportingInformationLineItems" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="presentation: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to RevenueFromContractWithCustomerExcludingAssessedTax" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="CostsAndExpenses" xlink:title="presentation: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to CostsAndExpenses" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="OperatingIncomeLoss" xlink:title="presentation: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to OperatingIncomeLoss" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.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="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="Assets" xlink:title="presentation: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to Assets" 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="SegmentReportingInformationLineItems" xlink:to="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="presentation: SegmentReportingInformationLineItems to SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" 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="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:to="SegmentReportingInformationLineItems" xlink:title="presentation: ScheduleOfSegmentReportingInformationBySegmentTable to SegmentReportingInformationLineItems" 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="SegmentReportingAbstract" xlink:to="ScheduleOfSegmentReportingInformationBySegmentTable" xlink:title="presentation: SegmentReportingAbstract to ScheduleOfSegmentReportingInformationBySegmentTable" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>GRAPHIC
<SEQUENCE>13
<FILENAME>image00001.jpg
<TEXT>
begin 644 image00001.jpg
M_]C_X  02D9)1@ ! 0$ 8 !@  #_VP!#  8$!08%! 8&!08'!P8("A *"@D)
M"A0.#PP0%Q08&!<4%A8:'24?&ALC'!86("P@(R8G*2HI&1\M,"TH,"4H*2C_
MVP!# 0<'!PH("A,*"A,H&A8:*"@H*"@H*"@H*"@H*"@H*"@H*"@H*"@H*"@H
M*"@H*"@H*"@H*"@H*"@H*"@H*"@H*"C_P  1"  \ )T# 2(  A$! Q$!_\0
M'P   04! 0$! 0$           $" P0%!@<("0H+_\0 M1   @$# P($ P4%
M! 0   %] 0(#  01!1(A,4$&$U%A!R)Q%#*!D:$((T*QP152T? D,V)R@@D*
M%A<8&1HE)B<H*2HT-38W.#DZ0T1%1D=(24I35%565UA96F-D969G:&EJ<W1U
M=G=X>7J#A(6&AXB)BI*3E)66EYB9FJ*CI*6FIZBIJK*SM+6VM[BYNL+#Q,7&
MQ\C)RM+3U-76U]C9VN'BX^3EYN?HZ>KQ\O/T]?;W^/GZ_\0 'P$  P$! 0$!
M 0$! 0        $" P0%!@<("0H+_\0 M1$  @$"! 0#! <%! 0  0)W  $"
M Q$$!2$Q!A)!40=A<1,B,H$(%$*1H;'!"2,S4O 58G+1"A8D-.$E\1<8&1HF
M)R@I*C4V-S@Y.D-$149'2$E*4U155E=865IC9&5F9VAI:G-T=79W>'EZ@H.$
MA8:'B(F*DI.4E9:7F)F:HJ.DI::GJ*FJLK.TM;:WN+FZPL/$Q<;'R,G*TM/4
MU=;7V-G:XN/DY>;GZ.GJ\O/T]?;W^/GZ_]H # ,!  (1 Q$ /P#ZIHJ*ZN8+
M2+S;J>*"/.-\CA1GZFJT&L:;/*L4&HV<DK'"HDZL3] #0-1;5TB]112,P52S
M$!0,DDX H$+17/W7C3PU:RF.?7M-20<%?M"DC\C6CI>LZ9JJEM,U"TNP.OD3
M*^/K@T%NE.*NT[%^BBHKFXAM83+<S1PQ#J\C!5'XF@@EHJE;ZMIMS,L5OJ%G
M+*WW42968_0 U=H&TUN%([K&C.[!449+$X 'K5?4;ZUTVREN[^=(+:(;GD<X
M %>$>,_&-YXU6XCMIGTKPE VV>Y8?/<'LH'\1/9!]6('1I'=@LOJ8MWCI%;O
M]/-^1[+X:\267B-K]M+W2VMK+Y'VC^"5L9.WU R.>];=<E\/?[/TOP)IKK$F
MFVCKO43R $AB<,S' W,,'\<"M^'6-,GE6*'4;.21CA42=22?89I'/B*7+4E&
M"T3M]Q>HHJEJFK:?I,0DU.^MK1#T,\H3/TS08I.3LB[17,)X^\*.^T:_I^?>
M4 ?F:W[&^M+^'S;&Y@N8O[\,@<?F*"I4IP^)-%BBH9+JWCE\J2>)9, [&< \
M^U34$6/-?V@O^2=R_P#7S%_6O#/A(?\ BX^A?]=__937N?[0?_).Y?\ KYB_
MK7AGPD_Y*/H7_7?_ -E-6MCZ;+O]QG_V]^1]7:]J]IH6CW6I:C)LMK=-S'N?
M0#W)X%?*GCSX@:OXNNY!-,]OIV?W=G&V% [;O[Q]S^&*]-_:8U22+3]'TN-B
M(YW>>0#OMP%_]"->=_!SPM!XI\7K#?KOL;6,W$R9QOP0 OT)(S[ T16ER,MH
M4Z%!XJHM?Z_$Y&STO4+U"]G8W5P@ZM%$S@?D*CAFN]-O!)"\]K=1'AE)1T/\
MQ7V_;00VL"0VT4<,*#:J1J%51Z "N)^+7@^R\2>&;R<P(NIVL3303J,,=HSL
M)[@XQ[4<PZ6=QG/EG"R?F<Q\&OB;+KLRZ)X@D4ZAM_T>XZ>=@<JW^UCOW^O7
MH/CS_P DSU'_ *Z0_P#HQ:^7M,O)M.U*VO+5BL]O*LJ$'H0<BOIKXV7"W7PG
MNKA/NS?9Y!]"ZFAJS(Q6$C0Q=*<%92:^^Y\Q6=W/97<-S:2O%<0L'CD0X*L.
MA%?5WPL\<0^,M%_>E(]5MP%N8AQGT=1Z']#QZ5\G6\,MQ,L4$;22L<*BC))]
MA6CX8UV]\-ZU;ZEILFR>$\@]'7NI]0:;5ST\?@XXJ%OM+8^F?C+9V=WX?L_[
M2FE2UBNA(T<7WIB$;" ]!UZGH!T->;Q:2;^]L/[3MEQD)I^CQ@A%!/#2#J%[
MG/S-U)QS7=ZOXHMO%/@_3=2T>".:=I\%9B,6D@0EBV>.!R">.AKB_!7B:!OB
M-IFG:8XNWFE?[7J$@R93L8[8\\A<CENK>PZ^55EB*E=TJ>B6[[?YO\CFP-2I
MA\(T]X\VG];>N[V1VOQ\41_#655  6>$  8 YKPCX5G_ (N)H/\ U]+7O/[0
M/_).;C_KXB_G7@WPK_Y*)H/_ %]+7J1V,LM_W&?S_(^EOB;XH/A'PG<:A$JM
M=NPAMU;IO;/)]@ 3^%?)FH7^H:YJ37%[//>7D[8RQ+,Q/0 ?R KZ0_:$TFXU
M'P.D]JK/]BN%GD51GY-K*3^&1^&:^:]+O[C2]2MKZS<)<V\BRQL1G# Y'%$=
MBLFIP5!SC\1LW/@CQ/;6_G3:#J*QXR3Y#''U '%5/#,^LVVN6\>@2W,.I22"
M-%A)#%L]"/3USQ7K.B_'J955-:T=)#_%):R;?_'6S_.NX\)^*O!'B?7HK^R2
M"#7MA1?M$8CE8'J >C'\2<9IW?4NIC,32B_;4M/+5?,Z^PT^273;+^W!!=:A
M'&OFRJF%+CN!VZFM2BBLSY64G)W9YK^T'_R3N7_KYB_K7AGPD_Y*/H7_ %W_
M /937N?[0?\ R3N7_KYB_K7AGPD_Y*/H7_7?_P!E-6MCZ3+O]QG_ -O?D>F_
MM-:=(]KHNI("8XVD@<^A;!7_ -!:N$^"/B6V\-^,@=0<16EY$;=Y6Z1DD%2?
M;(Q^-?2WBC0[3Q'H=UI=^N89UQN'5&'(8>X-?)OC7P;JWA'4&@U&!FMRV(KE
M!F.4>Q['V/-"U5A9;5IXC#O"S>I]C(RNH9"&5AD$'((KD/BEXGM/#?A.]::5
M/MES$T-M#GYG9AC./09R3_C7R[IOBG7M+M_(T_6+^V@'2..=@H^@SQ6?=75Y
MJEYYEU-<7=S(<;I&+NWH.>:.4FEDG+44IRND,LK:6]O8+:W4O--(L:*.[$X
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HX8T7P^I&CZ;;VK$8+JN7(]V/)_.MBBG=FD\36J*TY-KU"BBBD8G_V0$!

end
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>GRAPHIC
<SEQUENCE>14
<FILENAME>image00002.jpg
<TEXT>
begin 644 image00002.jpg
M_]C_X  02D9)1@ ! 0$ 8 !@  #_VP!#  8$!08%! 8&!08'!P8("A *"@D)
M"A0.#PP0%Q08&!<4%A8:'24?&ALC'!86("P@(R8G*2HI&1\M,"TH,"4H*2C_
MVP!# 0<'!PH("A,*"A,H&A8:*"@H*"@H*"@H*"@H*"@H*"@H*"@H*"@H*"@H
M*"@H*"@H*"@H*"@H*"@H*"@H*"@H*"C_P  1" !/ &$# 2(  A$! Q$!_\0
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@4018WC20A957H&'>ML    8 X I %%%% !1110!__]D!

end
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>15
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6824332496">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br></strong></div></th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>Company</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and 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_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">4<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>16
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6667678928">
<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">9 Months Ended</th>
</tr>
<tr><th class="th">
<div>Sep. 30, 2019 </div>
<div>Segment</div>
</th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
<td class="nump">2<span></span>
</td>
</tr>
</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>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>17
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6829860800">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th" colspan="2"><div>Sep. 30, 2019</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 1,212<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,212<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">137<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(606)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">606<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,988,932<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,874,529<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,307<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">556<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,185)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(4,068)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,993,054<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,871,017<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">1,987,720<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,873,317<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,307<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">419<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(579)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(4,068)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,992,448<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,869,668<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">1,297,389<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,433,930<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,073<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">31<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(237)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(2,362)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,299,225<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,431,599<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember', window );">Available-for-sale Securities [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">690,331<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">439,387<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,234<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">388<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(342)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,706)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">693,223<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">438,069<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">752,495<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">956,879<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,484<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">13<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(148)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,858)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">753,831<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">955,034<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">539,820<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">299,018<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,108<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">194<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(161)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(1,286)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">542,767<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">297,926<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">176,589<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">168,839<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">321<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(45)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(104)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">176,865<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">168,738<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">106,536<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">107,789<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">101<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">194<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(137)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(109)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">106,500<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">107,874<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">331,371<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">244,640<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">264<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">15<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(17)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(77)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">331,618<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">244,578<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">34,692<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">15,600<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(38)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(24)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">34,654<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">15,576<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">33,986<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">63,572<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">4<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(27)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(323)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">33,963<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">63,249<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">9,283<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">16,980<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">25<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(6)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(287)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">9,302<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 16,693<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">2,948<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,948<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr><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">We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our 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 available-for-sale securities are held at amortized cost.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash equivalents 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_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_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=118939692&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=118939692&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=118939692&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=118942338&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 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118942338&amp;loc=SL82898722-210454<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118954083&amp;loc=d3e26610-111562<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 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI http://asc.fasb.org/extlink&amp;oid=118939692&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=99377092&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI). Excludes equity method investment and investment in equity security without readily determinable fair value.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=116654751&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=116654751&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_DebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_OtherDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>18
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6809173504">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 99,304<span></span>
</td>
<td class="num">$ (87,747)<span></span>
</td>
</tr>
<tr class="re">
<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 provided by operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Depreciation', window );">Depreciation</a></td>
<td class="nump">9,345<span></span>
</td>
<td class="nump">7,650<span></span>
</td>
</tr>
<tr class="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_OperatingLeaseRightOfUseAssetAmortization', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="nump">1,433<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of patents</a></td>
<td class="nump">1,139<span></span>
</td>
<td class="nump">1,356<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium (discount) on investments, net</a></td>
<td class="num">(7,064)<span></span>
</td>
<td class="nump">791<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">1,448<span></span>
</td>
<td class="nump">1,343<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AmortizationOfDebtDiscountPremium', window );">Amortization of convertible senior notes discount</a></td>
<td class="nump">26,747<span></span>
</td>
<td class="nump">24,781<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">111,564<span></span>
</td>
<td class="nump">97,210<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetImpairmentCharges', window );">Non-cash losses related to patents, licensing and property, plant and equipment</a></td>
<td class="nump">216<span></span>
</td>
<td class="nump">482<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefit', window );">Provision for deferred income taxes</a></td>
<td class="nump">4,103<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract', window );"><strong>Changes in operating assets and liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="num">(33,716)<span></span>
</td>
<td class="nump">48,223<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="num">(6,606)<span></span>
</td>
<td class="nump">1,604<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="num">(23,377)<span></span>
</td>
<td class="num">(26,573)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="num">(18,764)<span></span>
</td>
<td class="num">(13,606)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="num">(4,864)<span></span>
</td>
<td class="num">(892)<span></span>
</td>
</tr>
<tr class="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_IncreaseDecreaseInAccruedAndDeferredLiabilities', window );">Accrued liabilities and deferred rent</a></td>
<td class="nump">3,909<span></span>
</td>
<td class="num">(14,392)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="num">(97,029)<span></span>
</td>
<td class="nump">447,168<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash provided by operating activities</a></td>
<td class="nump">67,788<span></span>
</td>
<td class="nump">487,398<span></span>
</td>
</tr>
<tr class="ro">
<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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="num">(1,617,726)<span></span>
</td>
<td class="num">(1,156,335)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from short-term investments</a></td>
<td class="nump">1,465,600<span></span>
</td>
<td class="nump">568,517<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="num">(23,143)<span></span>
</td>
<td class="num">(12,221)<span></span>
</td>
</tr>
<tr class="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_PaymentsToAcquireLicensesAndOtherAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(4,196)<span></span>
</td>
<td class="num">(3,317)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash used in investing activities</a></td>
<td class="num">(179,465)<span></span>
</td>
<td class="num">(603,356)<span></span>
</td>
</tr>
<tr class="ro">
<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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity awards</a></td>
<td class="nump">112,137<span></span>
</td>
<td class="nump">18,254<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="num">(18,841)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from the issuance of common stock to Biogen</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">447,965<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RepaymentsOfLongTermDebt', window );">Principal payments on debt obligations</a></td>
<td class="num">(12,500)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by financing activities</a></td>
<td class="nump">80,796<span></span>
</td>
<td class="nump">466,219<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect', window );">Net increase in cash and cash equivalents</a></td>
<td class="num">(30,881)<span></span>
</td>
<td class="nump">350,261<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="nump">278,820<span></span>
</td>
<td class="nump">129,630<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">247,939<span></span>
</td>
<td class="nump">479,891<span></span>
</td>
</tr>
<tr class="re">
<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 " 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">5,474<span></span>
</td>
<td class="nump">5,434<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="nump">9,037<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract', window );"><strong>Supplemental disclosures of non-cash investing and financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability', window );">Right-of-use assets obtained in exchange for lease obligations</a></td>
<td class="nump">14,178<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">3,251<span></span>
</td>
<td class="nump">2,296<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CapitalExpendituresIncurredButNotYetPaid', window );">Purchases of property, plant and equipment included in long-term obligations</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 3,596<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInAccruedAndDeferredLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate amount of expenses incurred but not yet paid and deferred liabilities due within one year or operating cycle.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInAccruedAndDeferredLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NonCashCapitalAndPatentExpenditures">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NonCashCapitalAndPatentExpenditures</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_OperatingLeaseRightOfUseAssetAmortization">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<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 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>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_OperatingLeaseRightOfUseAssetAmortization</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PaymentsToAcquireLicensesAndOtherAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for acquisition of licenses and other assets not otherwise defined in the taxonomy.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentsToAcquireLicensesAndOtherAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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=118932676&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_AmortizationOfDebtDiscountPremium">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense included in interest expense to amortize debt discount and premium associated with the related debt instruments. Excludes amortization of financing costs. Alternate captions include noncash interest expense.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=114775744&amp;loc=d3e28541-108399<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&amp;loc=d3e3602-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfDebtDiscountPremium</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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=118932676&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=116634182&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=114775744&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=118932676&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_AssetImpairmentCharges">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of write-down of assets recognized in the income statement. Includes, but is not limited to, losses from tangible assets, intangible assets and 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 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&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 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=109226348&amp;loc=d3e2420-110228<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetImpairmentCharges</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CapitalExpendituresIncurredButNotYetPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Future cash outflow to pay for purchases of fixed assets that have occurred.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4332-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4313-108586<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=98513485&amp;loc=d3e4304-108586<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CapitalExpendituresIncurredButNotYetPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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=118932676&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=118932676&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=98513485&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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<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 and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; excluding effect from exchange rate change. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=98513438&amp;loc=d3e33268-110906<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI http://asc.fasb.org/extlink&amp;oid=116825942&amp;loc=d3e330036-122817<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<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=118932676&amp;loc=d3e3602-108585<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 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Depreciation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of expense recognized in the current period that reflects the allocation of the cost of tangible assets over the assets' useful lives. Includes production and non-production related depreciation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&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_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=98513485&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=118932676&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=118932676&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInAccountsPayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&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=118932676&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInInventories">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate value of all inventory held by the reporting entity, associated with underlying transactions that are classified as operating activities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInInventories</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOperatingCapitalAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in employer-related costs classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&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=118932676&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=98513485&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=118932676&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=118932676&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=118932676&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=118932676&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=118932676&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=118932676&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=118932676&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_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=118932676&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=118932676&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=118932676&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=118954083&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_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=118932676&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_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the additional capital contribution to the entity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&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=118932676&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=118932676&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=118932676&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=118954083&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<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=115929826&amp;loc=d3e8736-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591551-111686<br><br>Reference 7: 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 2<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&amp;loc=d3e3000-108585<br><br>Reference 8: 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 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591552-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfLongTermDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 debt initially having maturity due after one year or beyond the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&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_RepaymentsOfLongTermDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in right-of-use asset obtained in exchange for operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=77888399&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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=118932676&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>19
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6975836400">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.</div>

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

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

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

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

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. </span>In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Europe, prior to the third quarter of 2019 we distributed TEGSEDI through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL was our sole customer in Europe. The 3PL in Europe then distributed TEGSEDI to hospitals and pharmacies. In the third quarter of 2019, we entered into a distribution arrangement with a 3PL and began to sell both TEGSEDI and WAYLIVRA directly to hospitals and pharmacies in Europe.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide details about our collaboration agreements in Note 7, </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;"> in our Annual Report on Form 10-K for the year ended December 31, 2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za828ef045c5342ec950720727f58194e" 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z423ff748c87641c8b173de2f4fc02db9" 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" id="zf1c5606cc4d545ceaeee39b9216b6706" 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" id="zd1b38b04c6d44ee2a317b490bdd9a611" 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" id="zdc1a47e8a7f84ce9b17a88c78aaa2813" 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 is probable. </div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z154b7c49dc104a57ab977ae0e4e30809" 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;">2.</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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Often times 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. These items are contingent upon future events that may not occur. 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0c7f5c3635d344b3a58160ef8667cdcd" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when Roche dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx </sub>(RG6042). We did not consider these milestone payments probable until Roche achieved the milestone event because the dosing of a patient was a contingent event that was not within our control. We recognized the milestone payments in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payments.</div>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6b0a5e16e14f413e9cb3790671d564a2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
  </tr>
</table>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1050d76f512c44499a8a4a55c6cd90ec" 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" id="zc0968e72382e45d9a26ab5eae98b5ed7" 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 on future product sales;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zdc34827c6d5d41dabfa0b3a3713d80db" 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;">Contractual milestone payments;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc92b502b421a42638f6c4797795c4af4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses we expect to incur;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc9eaca6cecc84fc5a8f56282da85c4c1" 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;">Income taxes; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9f345c6a9ccf4de79419b350e5a3fc46" 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7a4859a1235b498a8927bb7e99a59f30" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of internal hours we estimate we will spend performing these services;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z479e033d5771475ab32e613cf9bf9239" 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" id="z781255f68a404a85aa0ec8ffb0f8d24f" 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" id="z6ce136f034fc4177890b3f2eae4d4f3a" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb5abc673cc6d48aa89e5180f190cfad5" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -54pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. For example, </span>in the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation under our<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2013 Strategic Neurology collaboration with Biogen</span>. As of September 30, 2019, we have completed a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> significant portion of the research and development services. We expect to complete the remainder of our services in 2020. As a result of our change in estimate, in the third quarter of 2019, we recorded a cumulative catch up adjustment of $</span>16.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to decrease revenue. We expect to complete the remainder of our services in 2020. Refer to Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further discussion of the cumulative catch up adjustment we made.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>

<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Commercial Revenue: Product sales, net</span></span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize product sales in the period </span>when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are the components of variable consideration related to product sales:</div>

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

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Chargebacks: </span>In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record reserves for these chargebacks related to product sales to our U.S. customer during the reporting period.</div>

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

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Government rebates</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">: We are subject t</span>o discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Trade discounts: </span>We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Distribution services</span>: We receive and pay for various distribution services from our U.S. and EU customers and wholesalers in the U.S. For services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value, we classify the costs for such services as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as selling, general and administration, or SG&amp;A, expenses.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Product returns: </span>Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#8217;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we believe we will have minimal returns. Our EU customers only take title to the product after they receive an order from a hospital or pharmacy and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in the EU and we do not estimate returns in the EU.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Other incentives: </span>In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale.</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Upfront payments</span></span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases</span>, 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced a new target for an unidentified neurological disease under our 2018 strategic neurology 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2019, we recognized an $8 million milestone payment <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">when Biogen initiated a Phase 1/2 study of IONIS-LRRK2</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (BIIB094) for the treatment of people with Parkinson&#8217;s disease</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payment was not related to our R&amp;D services performance obligation. Therefore, we recognized the milestone payment in full in the third quarter of 2019.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. </span>For example, in the third quarter of 2019, we earned a $25 million license fee when GSK licensed our HBV program from us.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. </span>For example, in the second quarter of 2019, we earned a $20 million sublicense fee when Alnylam Pharmaceuticals sublicensed our technology to Regeneron Pharmaceuticals.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd501d31562294c6aaa719422cd15d756" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3dd236033f64fc69c60fe14eb86f927" 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 at a stand-alone selling price. </div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 at their 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $</span>100<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million transaction price to these performance obligations. </span>Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for further discussion <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of our accounting treatment for our Bayer collaboration.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z647b2221962b4885b6203f5375ade9eb" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24d42ec8f51f41848c8f9d33210e47e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf3b846712a0f4085b6899ba8ff04e10d" 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ReceivablesPolicyTextBlock', window );">Contracts Receivable</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer</span>.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 " 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 September 30, 2019 and 2018, we recognized $30.3 million and $37.2 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the nine months ended&#160;September 30, 2019 and 2018, we recognized $103.5 million and $80.4 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Products Sold</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 Products Sold</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed a significant portion of the costs we incurred to produce the supply for each medicine we are using in the commercial launch as research and development expense. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We previously expensed $</span>0.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>0.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of costs to produce our products related to the product sales revenue we recognized in the</span>&#160;three and nine months ended September 30, 2019, respectively.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy', window );">Noncontrolling Interest in Akcea Therapeutics, Inc.</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;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to Akcea&#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#8217;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L<sub>Rx</sub> to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. At September 30, 2019, our ownership in Akcea was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx</sub>. We reflect changes in our ownership of Akcea in our financial statements as an adjustment to noncontrolling interest in the period the change occurs. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The shares third parties own represent an interest in Akcea&#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.</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_ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock', 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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. We use the specific identification method to determine the cost of securities sold.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 September 30, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market 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. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained the first regulatory approval for TEGSEDI in July 2018 and in May 2019 for WAYLIVRA. At September 30, 2019, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;D expenses.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did </span>no<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t record any material inventory write-offs for the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Total inventory was $</span>19.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>8.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million as of </span>September 30, 2019 and December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</span></div>

<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Topic 842 Adoption</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2016, the Financial Accounting Standards Board, or FASB, issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>, or Topic 840, and created a new lease accounting standard, Topic 842, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing lease, it will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. </span>The adoption did not have an impact on our condensed consolidated statement of operations.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determined the lease term at the inception of the 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.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 or as of the lease inception date in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpensePolicy', window );">Research and Development Expenses</a></td>
<td class="text"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">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.</span><span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IntangibleAssetsFiniteLivedPolicy', window );">Patent Expenses</a></td>
<td class="text"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">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 United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.</span><span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxPolicyTextBlock', window );">Income Taxes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock', window );">Long-Lived Assets</a></td>
<td class="text">
<div style="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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, 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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UseOfEstimates', window );">Use of Estimates</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Income (Loss) per Share</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Income (Loss) Per Share</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,221</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.34</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,772</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,772</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,930</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,551</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.40</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,174</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,174</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,938</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,538</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.73</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47,843</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47,843</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,346</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.03</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.93</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,680</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,680</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,517</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43,163</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.33</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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;">Dilutive net income (loss per share)</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.</div>

<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>
<span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the three months ended September 30, 2019</span><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"> as follows (in thousands except per share amounts):</span>
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,551</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,993</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">844</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,408</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the nine months ended&#160;September 30, 2019 as follows (in thousands except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,208</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">793</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">142,821</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.79</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended September 30, 2018, 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5651e0539b1741fda1231d28f3d75c17" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7e90304a08cb4b28bbe2c90004d5b48d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options; </div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z503eee239a9647d2b0c553764a10ff4d" 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; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7ddd358f5ffd49cb80e76497ec47f5cc" 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>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtPolicyTextBlock', window );">Convertible Debt</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is </span>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.</span></div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#160;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

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

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

<table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.1</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; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">45.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis RSU&#8217;s:</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year period. The weighted-average grant date fair value of RSUs granted to employees for the nine months ended&#160;September 30, 2019 was $59.79 per share. The weighted-average grant date fair value of RSUs granted to our board of directors for the nine months ended&#160;September 30, 2019 was $64.65 per share.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our stock plans, Akcea has its own stock plan under which it grants stock options and RSUs and under which it derives its stock-based compensation expense. <span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">&#160;</span></span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">September 30, 2019</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"> and 2018</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">: </span></div>

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

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

<table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.7</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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">75.6</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;">77.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">1.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">73.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.4 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;">Akcea ESPP:</span></div>

<table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands).</div>

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

<table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/>
    <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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">Cost of products sold</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,744</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,780</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,935</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,698</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">255</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,103</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,246</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total non-cash stock-based compensation expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,126</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,883</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111,564</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97,210</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2019, three Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $19.1 million of stock-based compensation expense it had previously recognized related to the executive officers&#8217; stock options and RSUs that were no longer going to vest.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $143.9 million and $71.3 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 non-vested stock options and RSUs over a weighted average amortization period of 1.2 years and 1.6 years, respectively.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of Recently Issued Accounting Standards</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. We plan to adopt this guidance on January 1, 2020 on a prospective basis. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.</div>

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

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

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8bdd29a294eb40de9936181c921e770a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcfd41a05fd534170aa5bf96451b5d895" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer </div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z01a3ba1f007c4a6aa41b051b55d3c310" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf0bc1b58e5944c7c95ca172b59ca15bd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We will use the &#8220;unit of account&#8221; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8b99d6ac86964c488e342898b48a042f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z991322bb7f8b47b487f7e37acfd889f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction </div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it could have on our condensed consolidated financial statements and disclosures.</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_CashCashEquivalentsAndInvestmentsPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 cash, cash equivalents and 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;">ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 subsidiaries or other investments that are consolidated, including the accounting treatment for intercompany accounts or transactions and any noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=d3e5614-111684<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.3A-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=116822174&amp;loc=d3e355100-122828<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&amp;loc=d3e23780-122690<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section S99<br> -Paragraph 4<br> -Subparagraph (SX 210.3A-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=116822174&amp;loc=d3e355119-122828<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.3A-02)<br> -URI http://asc.fasb.org/extlink&amp;oid=116822174&amp;loc=d3e355033-122828<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6802200&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3630-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32847-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 954<br> -SubTopic 740<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6491622&amp;loc=d3e9504-115650<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32809-109319<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 1<br> -URI http://asc.fasb.org/extlink&amp;oid=116657188&amp;loc=SL116659661-227067<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32840-109319<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<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=116821951&amp;loc=d3e32247-109318<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<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=116821951&amp;loc=d3e32280-109318<br><br>Reference 9: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 30<br> -Section 05<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=65884525&amp;loc=d3e40913-109327<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of inventory accounting policy for inventory classes, including, but not limited to, basis for determining inventory amounts, methods by which amounts are added and removed from inventory classes, loss recognition on impairment of inventories, and situations in which inventories are stated above cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4556-108314<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6361739&amp;loc=d3e7789-107766<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=116846552&amp;loc=d3e543-108305<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<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 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 210.5-02.6(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=77888426&amp;loc=SL77918666-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeLeasesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy pertaining to new accounting pronouncements that may impact the entity's financial reporting. Includes, but is not limited to, quantification of the expected or actual impact.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReceivablesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for receivable. Includes, but is not limited to, accounts receivable and financing receivable.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=118936363&amp;loc=d3e5033-111524<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10178-111534<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10149-111534<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10133-111534<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReceivablesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpensePolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for costs it has incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpensePolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue from contract with customer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -URI http://asc.fasb.org/topic&amp;trid=49130388<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueRecognitionPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue. Includes revenue from contract with customer and from other sources.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18823-107790<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueRecognitionPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b),(f)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&amp;loc=d3e5070-113901<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>20
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6815633712">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureTextBlock', window );">Income Taxes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Income Taxes</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 24.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded an income tax benefit of $14.9 million and an income tax expense of $9.2 million for the three and nine months ended&#160;September 30, 2019, compared to income tax expense of $0.5 million and $0.8 million for the same periods in 2018, respectively. The tax benefit recorded for the three months ended September 30, 2019 varies from what we would have recorded using the U.S. federal statutory rate primarily due to a state tax benefit resulting from our combined state tax filings with Akcea, estimated R&amp;D and orphan drug credits, excess tax benefits related to share-based compensation and a benefit related to a change in the estimated tax value of Akcea shares we received in 2018. The increase in our income tax expense for the nine months ended&#160;September 30, 2019, compared to the same period in 2018, was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019. We expect to utilize our deferred tax assets to partially offset our U.S. federal taxable income.</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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -URI http://asc.fasb.org/topic&amp;trid=2144680<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>21
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6817052960">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockParOrStatedValuePerShare', window );">Common stock, par value (in dollars per share)</a></td>
<td class="nump">$ 0.001<span></span>
</td>
<td class="nump">$ 0.001<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">140,636,397<span></span>
</td>
<td class="nump">137,928,828<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">140,636,397<span></span>
</td>
<td class="nump">137,928,828<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Face amount or stated value per share of common stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockParOrStatedValuePerShare</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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://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=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_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>EXCEL
<SEQUENCE>22
<FILENAME>Financial_Report.xlsx
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
begin 644 Financial_Report.xlsx
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MMWF\81AU8\K(XK%T-8943OTJDH\ Q:X831F:3LTXXFBD(3^ G/,6+V2?$9/
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M^L/O)FQ[;?;F'QM?!=L&?MU%^P502P,$%     @ 17UF3YE<G",0!@  G"<
M !,   !X;"]T:&5M92]T:&5M93$N>&UL[5I;<]HX%'[OK]!X9_9M"\8V@;:T
M$W-I=MNTF83M3A^%$5B-;'EDD81_OT<V$,N6#>V23;J;/ 0LZ?O.14?GZ#AY
M\^XN8NB&B)3R>&#9+]O6N[<OWN!7,B0103 9IZ_PP JE3%ZU6FD PSA]R1,2
MP]R"BPA+>!3+UES@6QHO(];JM-O=5H1I;*$81V1@?5XL:$#05%%:;U\@M.4?
M,_@5RU2-9:,!$U=!)KF(M/+Y;,7\VMX^9<_I.ATR@6XP&U@@?\YOI^1.6HCA
M5,+$P&IG/U9KQ]'22(""R7V4!;I)]J/3%0@R#3LZG5C.=GSVQ.V?C,K:=#1M
M&N#C\7@XMLO2BW <!.!1NY["G?1LOZ1!";2C:=!DV/;:KI&FJHU33]/W?=_K
MFVB<"HU;3]-K=]W3CHG&K=!X#;[Q3X?#KHG&J]!TZVDF)_VN:Z3I%FA"1N/K
M>A(5M>5 TR  6'!VULS2 Y9>*?IUE!K9';O=05SP6.XYB1'^QL4$UFG2&98T
M1G*=D 4. #?$T4Q0?*]!MHK@PI+27)#6SRFU4!H(FLB!]4>"(<7<K_WUE[O)
MI#-ZG7TZSFN4?VFK :?MNYO/D_QSZ.2?IY/734+.<+PL"?'[(UMAAR=N.Q-R
M.AQG0GS/]O:1I24RS^_Y"NM./&<?5I:P7<_/Y)Z,<B.[W?98??9/1VXCUZG
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M'%1J9_K7J7UOK^W<=6#T<6A5D[%?7OX!4$L#!!0    ( $5]9D^H&EX\AP0
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MR5&&*WX&Z*F2G^EP)Y<$.X"ZH."\7#N 2U636?)#]CR3FR@A--'22%<AFD@
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MN35!,,M3FTJ#"Z$!A=!,+1,N-<;_0(QQJ3% 8>L8!U48/5.4&A3 <LZ-U*
M9GP>C,IBC6-V+L@]TN+D=&);-4_#45$[NZ]?=ET?G).GQ^.H#]R?;HCG2[HJ
M"#R_HZO5X;#IN_G#V==O9?.TWK6SSW77U=OAY..QKKLJN9]=IO1XKLJ'X\VF
M>NSZ2Y^NF\.9T^&FJ_?C>=KB>*AW^R]02P,$%     @ 1GUF3X^WAF7- @
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M68]ATS@88V1)<U$.T]K%1/IGR0+")?2=!8] 41$@RBI>%@&BK'17 ,8^:&L
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M66>E(ZW+U$2<>;8&;(R2C:RA)U<JD"121Y^A!V,N,B@XHZS'69>2:046"AY
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MV&HH:%PXOO-G,X_9;#@<EA_$UF]<_@902P,$%     @ 1GUF3P-P]1VT 0
MT@,  !D   !X;"]W;W)K<VAE971S+W-H965T,3 N>&UL?5-A;]P@#/TKB!]0
M+B3=JE,2J==JVJ1-.G7:]IE+G 05X@S(I?OW Y)FV1;U"V#C]_QL3#ZA>;8=
M@",O6O6VH)USPY$Q6W6@A;W! 7I_TZ#1PGG3M,P.!D0=05HQ?CB\8UK(GI9Y
M])U-F>/HE.SA;(@=M1;FUPD43@5-Z*OC2;:="PY6YH-HX2NX;\/9>(NM++74
MT%N)/3'0%/0^.9ZR$!\#ODN8[.9,0B47Q.=@?*H+>@B"0$'E H/PVQ4>0*E
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MN'!\[\]F'K/9<#@L/XBMW[C\#5!+ P04    " !&?69/L=ZSF;4!  #2 P
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M+9[M.&:CX4TW_2 V?^/\ U!+ P04    " !&?69/#B=H%+0!  #2 P  &0
M 'AL+W=O<FMS:&5E=',O<VAE970Q,BYX;6Q]4]MNW" 0_17$!P2;W;;;E6TI
MFZIJI49:I6KRS-IC&P6,"WB=_'T'[#A6:_4%F.&<,Q>&;#3VV;4 GKQHU;F<
MMM[W1\9<V8(6[L;TT.%-;:P6'DW;,-=;$%4D:<5XDGQD6LB.%EGTG6V1F<$K
MV<'9$C=H+>SK"909<YK2-\>#;%H?'*S(>M' 3_"_^K-%BRTJE=30.6DZ8J'.
MZ6UZ/.T#/@(>)8QN=2:ADHLQS\'X7N4T"0F!@M('!8';%>Y J2"$:?R>->D2
M,A#7YS?UK[%VK.4B'-P9]20KW^;T0$D%M1B4?S#C-YCK^4#)7/P/N()">,@$
M8Y1&N;B2<G#>Z%D%4]'B9=IE%_=QNN&'F;9-X#.!+X1#C,.F0#'S+\*+(K-F
M)';J?2_"$Z='CKTI@S.V(MYA\@Z]UX*GGS-V#4(SYC1A^ J3+@B&ZDL(OA7B
MQ/^A\VWZ;C/#7:3OUG2>; OL-P7V46#_WQ(W,/SO(MFJIQIL$Z?)D=(,79SD
ME7<9V%L>W^0=/DW[O;"-[!RY&(\O&_M?&^,!4TEN<(1:_&"+H:#VX?@)SW8:
ML\GPII]_$%N^<?$'4$L#!!0    ( $9]9D\>XT-EM $  -(#   9    >&PO
M=V]R:W-H965T<R]S:&5E=#$S+GAM;'U3VV[4,!#]%<L?4.]Z4ZA62:1N*P02
M2*LBZ+,WF216?0FVLRE_S]A)0X"(%]LSGG/FS'B<C]:]^ X@D%>MC"]H%T)_
M9,Q7'6CA;VP/!F\:Z[0(:+J6^=Z!J!-(*\9WNW=,"VEHF2??V96Y'8*2!LZ.
M^$%KX7Z>0-FQH'OZYGB2;1>B@Y5Y+UKX"N%;?W9HL86EEAJ,E]80!TU![_?'
M4Q;C4\!W":-?G4FLY&+M2S0^U07=14&@H J10>!VA0=0*A*AC!\S)UU21N#Z
M_,;^(=6.M5R$AP>KGF4=NH+>45)#(P85GNSX$>9Z;BF9B_\,5U 8'I5@CLHJ
MGU92#3Y8/;.@%"U>IUV:M(_3#<]FV#: SP"^ .Y2'C8E2LH?11!E[NQ(W-3[
M7L0GWA\Y]J:*SM2*=(?B/7JO)><\9]=(-,><IAB^BMDO$0S9EQ1\*\6)_P/G
MV_##IL)#@A_^4'C8)L@V";)$D/VWQ*V8[*\D;-53#:Y-T^1)90>3)GGE70;V
MGJ<W^1T^3?L7X5II/+G8@"^;^M]8&P"E[&YPA#K\8(NAH GQ^![/;AJSR0BV
MGW\06[YQ^0M02P,$%     @ 1GUF3X("2>6U 0  T@,  !D   !X;"]W;W)K
M<VAE971S+W-H965T,30N>&UL?5-A;]L@$/TKB!]0$I*F561;:EI5F[1)4:=M
MGXE]ME&!\P#'W;\?8-?S-FM?@#ONO7MW'-F ]M6U )Z\:65<3EOONR-CKFQ!
M"W>#'9AP4Z/5P@?3-LQU%D250%HQOMD<F!;2T")+OK,M,NR]D@;.EKA>:V%_
MGD#AD-,M?7>\R*;UT<&*K!,-? '_M3O;8+&9I9(:C)-HB(4ZIP_;XVD?XU/
M-PF#6YQ)K.2"^!J-CU5.-U$0*"A]9!!AN\(C*!6)@HP?$R>=4T;@\OS._IQJ
M#[5<A(-'5-]EY=N<WE-202UZY5]P^ !3/;>43,5_@BNH$!Z5A!PE*I=64O;.
MHYY8@A0MWL9=FK0/X\UA-\'6 7P"\!EPG_*P,5%2_B2\*#*+ [%C[SL1GWA[
MY*$W972F5J2[(-X%[[7@_#9CUT@TQ9S&&+Z(V<X1++#/*?A:BA/_!\[7X;M5
MA;L$W_VA\+!.L%\EV">"_7]+7(NY^RL)6_14@VW2-#E28F_2)"^\\\ ^\/0F
MO\/':?\L;".-(Q?TX653_VM$#T'*YB:,4!L^V&PHJ'T\WH6S'<=L-#QVTP]B
M\S<N?@%02P,$%     @ 1GUF3V@P&G:T 0  T@,  !D   !X;"]W;W)K<VAE
M971S+W-H965T,34N>&UL?5-ACY0P$/TK37_ %<JJZP9(;L\83339G%$_=V&
MYEH&V[*<_]ZV<(A*_-)VIO/>O)E.\PG-D^T ''G6JK<%[9P;3HS9J@,M[!T.
MT/N;!HT6SINF978P(.H(THKQ)'G-M) ]+?/HNY@RQ]$IV</%$#MJ+<S/,RB<
M"IK2%\>C;#L7'*S,!]'"%W!?AXOQ%EM9:JFAMQ)[8J IZ'UZ.A]"? SX)F&R
MFS,)E5P1GX+QL2YH$@2!@LH%!N&W&SR 4H'(R_BQ<-(U90!NSR_L[V/MOI:K
ML/" ZKNL75?0(R4U-&)4[A&G#[#4\XJ2I?A/< /EPX,2GZ-"9>-*JM$ZU N+
MEZ+%\[S+/N[3?).E"VP?P!< 7P''F(?-B:+R=\*),C<X$3/W?A#AB=,3][VI
M@C.V(MYY\=9[;R7GQYS= M$2<YYC^"8F72.89U]3\+T49_X/G._#LUV%681G
M?RA\NT]PV"4X1(+#?TO<B<F2OY*P34\UF#9.DR45CGV<Y(UW'=A['M_D=_@\
M[9^%:65OR16=?]G8_P;1@9>2W/D1ZOP'6PT%C0O'-_YLYC&;#8?#\H/8^HW+
M7U!+ P04    " !&?69/C 6?G,4!   W!   &0   'AL+W=O<FMS:&5E=',O
M<VAE970Q-BYX;6QU5-%NVR 4_17$!Q0')VT4V9::3M,F;5+4:>LSL:]M5# N
MX+C[^P%V73=E+P8NYYQ[+G"=C4H_FQ; HE<I.I/CUMK^0(@I6Y#,W*@>.K=3
M*RV9=4O=$--K8%4@24%HDMP2R7B'BRS$3KK(U& %[^"DD1FD9/KO$80:<[S!
M;X%'WK36!TB1]:R!7V!_]R?M5F11J;B$SG#5(0UUCN\WA^/.XP/@#X?1K.;(
M5W)6ZMDOOE<Y3KPA$%!:K\#<<($'$,(+.1LOLR9>4GKB>OZF_C74[FHY,P,/
M2CSQRK8YWF-40<T&81_5^ WF>G88S<7_@ L(!_=.7(Y2"1.^J!R,57)6<58D
M>YU&WH5QG';2=*;%"70FT(6P#WG(E"@X_\(L*S*M1J2GL^^9O^+-@;JS*7TP
M'$78<^:-BUX*FFXR<O%",^8X8>@*\XX@3GU)06,ICO03G<;I:=1A&NCIFI[L
MXP+;J, V"&P_"-Q=E1C!I/]QN8LFV44$TJLD,<SV*@E979P$W80G:U"IABZT
MRRJZ=,4]#1?_#I]:ZB?3#>\,.BOKGD^XY%HI"\Y*<N.\M*Z+EX6 VOKIG9OK
MZ2U/"ZOZN4W)\J\H_@%02P,$%     @ 1GUF3Z&#<=&J @  % L  !D   !X
M;"]W;W)K<VAE971S+W-H965T,3<N>&UL=5;;CMHP%/R5*!^PCAT2+@*D9:NJ
ME5H);=7MLQ<,1)O$J6U@^_>UG6Q*S?B%Q,Z<F>/+',[R*M6;/@EADO>F;O4J
M/1G3+0C1NY-HN'Z0G6CMEX-4#3=VJ(Y$=TKPO0]J:L*RK"0-K]ITO?1S6[5>
MRK.IJU9L5:+/3</5GXVHY765TO1CXKDZGHR;(.MEQX_BAS _NZVR(S*R[*M&
MM+J2;:+$894^TL6&,1?@$2^5N.J;]\0MY57*-S?XNE^EF<M(U&)G' 6WCXMX
M$G7MF&P>OP?2=-1T@;?O'^R?_>+M8EZY%D^R_E7MS6F5SM)D+P[\7)MG>?TB
MA@45:3*L_INXB-K"72968R=K[7^3W5D;V0PL-I6&O_?/JO7/:_^E8$,8#F!#
M !L#9EZ']$(^\T_<\/52R6NB^LWON#MCNF!V;W9NTF^%_V:3UW;VLF9YL207
M1S1@-CV&W6#HB""6?91@2&+#[L(9#L]AAKD/SV_#:41_ @DFGF#RWQ++8(D(
M,\4B!10I ,$L$$&8.18IH4AY3S#) A&$B6S7%(I, 0$+1! FQR(S*#(#!)-
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M!2<NI[&8T[[[] M.6MU8T=#=L[]02P,$%     @ 1GUF3^[^#'P6!   >!0
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M#8Z,9TJQ)DE'5),&#<B2R"PFC1I4$PM%8+9* $8#<WY7$$PPCDPRA?OJ'65
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MB_'XLK'_C3$>4$IR@R/4X0=;#06-#\=W>+;SF,V&-\/R@]CZC<L_4$L#!!0
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MTS\%#$KCMG=VKX89& (CVW&\R?0?D_T#4$L#!!0    ( $9]9D^G>B+[50(
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MNAPUFZ0Q2<.7+?)%BWS!8OM@D?]G\3@%NSGW^%O_$.XDC2='&_ 3IH-NK0V
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M6F\2?+%" V;?8\())A@1V*B/%N&2Q3Z<T<-;@\,<$6^7':+%)B+'CVZ:^(_
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M73B^\V>3QBP93@_S#R++-Z[^ %!+ P04    " !&?69/1UP:[=H%  !Q(@
M&0   'AL+W=O<FMS:&5E=',O<VAE970S-2YX;6R56MMNXS80_17#[XW%JZ3
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MW)(504JVJEJIE:*MVCX[9!+0 J:V$[9_7]L0RL+P$MO#F7-FG!E/VG'Q)@L
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MSH \]8);;$!" [(SH 9#M<%0#QC3878=QK @'+<QADOEL2<*>J* )PX;T-"
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M7+?_MG. \G 0]G!1%_NKPRG?Q?&H\?5_4$L#!!0    ( $9]9D]Y[4,&=@0
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M8PF(@NRC$$BZ$P2!W"46@K0[-1#(DQ;'^LNI_NK00VF.%8ZS\<7E6.$X'T%
M"SJ>33&+"/\ + +2 6#-.IL0^@%<N]#ZYC#'^LNI_NK0LQ'B6#FYO*#,6.?X
M&)WC0)>4HF6FLB2 R@%O,:HR]::U5R@XUCA.-4Y(WTL*UAH>75!DK#6<[JJ$
M=/)]L*#A(G%BX>)8E#@0 '=#>6=!@P'UO*!@C1! (YBS=MP)L$=3OG0$5A)!
M]TJ:<;<C-CH=+#:"BHUFKI);D/*ET\_N<ZAA.)[W/R -S+/'%%@:Q 72(+ T
M""H-FBFW*)3,*N946\_CAB%A.@M$9\_[C<!T%A?066 Z"TIGJID6=)SP'TS[
M9P)FLT!L)F- V=R\HX,Q.(L;'BU@ZDM*?2$]DU-B4LL+M@<2,U:.V1Y(RL78
MGR[FHD1<U!X7GM.8"[@H,1?EF&5:4HYIX4T7,TR"EP(B[))NXOT:)S$/)=C"
M$\F5X$@#;-S.PH8!859+RFK-?*.$V2HO./Q0F%T*+:PNX14]AI"@+&=APX P
M5Q5:@#UO PIS55UP6*$P"Q5B(2F+H/MWNDU]/ OK PJ.3M-S4[YU7UNJR:)X
MW]9M,D>MAR\Z-[P]C7?:;]G5 P/MC^SJJ3^]_^V^_WST=UJ^;;;5Y+6HZR+O
M3NI715&;)OKP2S.<:Y,N#P^96=7M;=3<E_UGF_ZA+G;VDU1P^"XV_Q]02P,$
M%     @ 1GUF3T1Y4>C] 0  <04  !D   !X;"]W;W)K<VAE971S+W-H965T
M-#0N>&ULC53;CILP$/T5Q >LN03(1H"T256U4BM%6W7[[,!PT=J8VB9L_[ZV
M(2P-;M67V![.969B3SHR_BH: .F\4=*)S&VD[ \(B:(!BL4#ZZ%37RK&*9;J
MR&LD>@ZX-"1*4.!Y,:*X[=P\-;$SSU,V2-)V<.:.&"C%_-<1"!LSUW=O@>>V
M;J0.H#SM<0W?0'[OSUR=T*)2MA0ZT;+.X5!E[I-_..TUW@!>6AC%:N_H2BZ,
MO>K#YS)S/9T0$"BD5L!JN<()"-%"*HV?LZ:[6&KB>G]3_VAJ5[5<L( 3(S_:
M4C:9NW>=$BH\$/G,QD\PUQ.YSES\%[@"47"=B?(H&!'FURD&(1F=550J%+]-
M:]N9=9SU;S0[(9@)P4)0WO\BA#,A?"?L3/%39J;4#UCB/.5L=/CT9_58WPG_
M$*IF%CIH>F>^J6J%BE[SV'],T54+S9CCA E6F#"(%PQ2^HM)8#,Y!EN!/RU.
M6T1@-PBM582&'J[HT6-B%]A9!79&8+=N@^?=Y3AA8H/I#,9/(KM)9#6)MB;^
M?2.BC4G@V3UBJT>\]?B;0&(52/Z_E7NKP-Z2@7]WH_;;5MXGB58WF *OS6,7
M3L&&S@R:5729)T^!>0'O\&D8?<6\;COA7)A4[\C<]HHQ"2H3[T$UO%'S;SD0
MJ*3>)FK/IRDP'23KYP&'EBF;_P902P,$%     @ 1GUF3XVZ/KU- P  8@X
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M?@WU>]G>>MH/)0_=C<Z[7"NG_P%02P,$%     @ 1GUF3UC\EHEX P  U0\
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M-)/*XT]/:@^:.G \O[%_,8=7A]D303-6_2X/LEC9D6T=Z)&<*_G,KE]I?Z#
MMOK3?Z<76BFXSD1IY*P2YM?*ST*RNF=1J=3DK1O+QHS7GO\6!@?@/@ / 4K[
M?P%>'^ ]&N#W ?Y[@+'?Z8YBO-D22=*$LZO%N]?;$OT5H2=?N9_K36.V>:;L
M$6KWDH9^E#@73=1C-AT&CS >#C]BLCD&N=Z <50.0R(82F2#YR(3"0"!)I@M
MA/'A-#S0#\\0>"."(%["!#Y(X!L"_X.A\23+#A,:3&,PRP#6"$"-8*;AX:D3
M'28>:>!%!(N$H$@X/TC@P@1+D&#YN)412!!];F46S:Q$^(Z7,2@2?^YE%L^\
M#!<Q+()<N,Q<P$UTA^).I:+'_41@C:T1!K+ TVK',TOQO1>/X")"'J#C376\
M^:OSW'M"<+$AH-H"?RH$@:;?B#.Z,&O*3Z89"2MGYT;J"V6T.S2\-=87[F0_
MTXW07,3O-%T7_4'XJ6R$M6=27>?FTCTR)JG*T5VH<BU4XQX6%3U*/5VJ.>^Z
M5[>0K.T[LS/\/4C_ 5!+ P04    " !&?69/NY +B& (  #^,@  &0   'AL
M+W=O<FMS:&5E=',O<VAE970T.2YX;6R56UUSXK@2_2L4[[-87]U2*DG5!)C,
M3.U63>W6O?>929R$6L"YX$QV__W:X&%Q?X#\$L Y:JM;TND^DGW]7FW_W+V4
M93WZ:[W:[&[&+W7]>C69[!Y>RO5B]TOU6FZ:_SQ5V_6B;GYNGR>[UVVY>-PW
M6J\FMBA@LEXL-^/;Z_VU;]O;Z^JM7BTWY;?M:/>V7B^V?]^5J^K]9FS&/R_\
MOGQ^J=L+D]OKU\5S^4=9_^?UV[;Y-3E:>5RNR\UN66U&V_+I9OS17'U-1=M@
MC_COLGS?G7P?M:Y\KZH_VQ]?'F_&1=NC<E4^U*V)1?/QHYR6JU5KJ>G'_SNC
MX^,]VX:GWW]:_[1WOG'F^V)73JO5_Y:/]<O-.(Y'C^73XFU5_UZ]?RX[A\)X
MU'G_:_FC7#7PMB?-/1ZJU6[_=_3PMJNK=6>EZ<IZ\=?A<[G9?[YW]G\VDQO8
MKH$]-K#F; /7-7"Y#7S7P/_;()YM$+H&(?<.T#6 8P/CSS; K@'FWB%V#6+N
M'5+7(.4V,,7/D2M(D\EAR/=S:+:H%[?7V^I]M#TL@]=%N]K,E6FGZ4-[=3\K
M]_]LYM&NN?KC%@)<3WZTECK,W0%C3S"F<'W,3, <$9.F"\=^6+$?=Y:U=S;U
M[S$5,([V@V,@8!\SS[#S2< 8W\?<2W9L'_-9LA/ZF"\2AHS!5PF#<H2=/-)N
M;\&=6+ G$>Y9\+(%O[?@>[&-)/X'3-AC-H>[R/<(\CU"?B]!M@"LEZ:@,_J
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MJCO5X*LQNW.0)#DE=1-87O P+'F>J4@\O[R@>:8([T8\,G!(4CKYA%7J(M6
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M)KKZ?'(&+!3LUQG*Q69Z> \F#TTS.?P<22XVBP];*=:)CC;"H\-2"!(.:'W
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M&:AI=K*BVNM1^ZNH<1KDU:A?XI;"B_.,V(A#'\L.^5TGW:XR7!BA^T0)/3J
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MNC4UK(0"Q!A&BQD3A2/R%C*[<IUP)-3:9.I[+M1PMJ)^8.W!"BME[45<I6Q
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MM)%@J[ :'9]A=)@4G1<$-^!/;Z5+D4555Q(=T=E!HN3NWJ=>S(/%4=]<7Z[
MCH=NC]O4GR-"W7+R1N]S*< 3AI!0"3\()$Z(9UC$LQ!]&SBZ@NDUJ&<"9#KT
ML?D%\2Q7"!,-!<SRNL4@ [4L9.=+,T28#NMW1@G3? 1"?;I%'EJ=$..H"2J-
M..CPOE-^"%]WUQ'2HJ(#90)4AN^I9LI/'J_O>IF=-&BBE-CY/0%FWG& X3M,
M+D \<WIR?HCN7X+\9SF3UN#_S_LH_L?#?GPV':*R%I]-SE">]\XF$?]J$$\&
MO9,WE1<%@P4"I%5D]<:C>#B91@,P6)Z?#6$X_,ED-#PP6$UXT@P'@UX\&/?
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MD^G'PW[WA&+:(N 0MM(3N[BE8%3_+.Z/SBA$_?+D@E*.35K <X1"^DCAH5W
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M=5(7J09KS12DY\A5;3BK $5"^&Q;Q=RLE5H3AR/&KK*F;TKL(;R/UDOI1#\
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M)F\T%2TQX>@^A@9LM6FZ=XM:&GZ Z ?%=^Y200R#APG%3ZU4HI,O,Q2,[)]
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M(XFVZ,FZQO,G(-E^JZ_8T#RCB"U@:FEM8J4/$2)(VJ@1J4WL\H7VDVXCEPL
MNL9M<W<Z."9)Y!"&28LJD!H&PN?:P9DLVR <1KA1"P'4[KGV+W!N)T)_IQ@O
M\M$GQ%Z1+0#U XYVOG'?XM T(R*9HL< WN@]^T8?L)"X _ 03/MOE"8@4!H
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MS;MK0<2[A)T&!A1FH [0.ZQ+@-[Y@+&ZL$4[#LGK ?<ZVGX,Z%\'3:+:E4B
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M$VM%RK9-"(PS(S^ @F\$\8:@#%R%9Q1C)^]W@@9L(9;70@G,:T1+8715@25
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MM-9E\U>23V,6^_FL^]]W\@U02P$"% ,4    " !%?69/'R// \     3 @
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M2P$"% ,4    " !%?69//3)MQ1X"  "6!@  &               @ $C$0
M>&PO=V]R:W-H965T<R]S:&5E=#,N>&UL4$L! A0#%     @ 1GUF3RP3MQJ-
M!0  X!L  !@              ( !=Q,  'AL+W=O<FMS:&5E=',O<VAE970T
M+GAM;%!+ 0(4 Q0    ( $9]9D^/MX9ES0(  -$)   8              "
M 3H9  !X;"]W;W)K<VAE971S+W-H965T-2YX;6Q02P$"% ,4    " !&?69/
M?)K]9*@(  #+.   &               @ $]'   >&PO=V]R:W-H965T<R]S
M:&5E=#8N>&UL4$L! A0#%     @ 1GUF3ZG::$DM!0  I1D  !@
M     ( !&R4  'AL+W=O<FMS:&5E=',O<VAE970W+GAM;%!+ 0(4 Q0    (
M $9]9D\XV X6M0$  -(#   8              "  7XJ  !X;"]W;W)K<VAE
M971S+W-H965T."YX;6Q02P$"% ,4    " !&?69/^XCFK+,!  #2 P  &
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M970Q,RYX;6Q02P$"% ,4    " !&?69/@@))Y;4!  #2 P  &0
M    @ '_-0  >&PO=V]R:W-H965T<R]S:&5E=#$T+GAM;%!+ 0(4 Q0    (
M $9]9D]H,!IVM $  -(#   9              "  >LW  !X;"]W;W)K<VAE
M971S+W-H965T,34N>&UL4$L! A0#%     @ 1GUF3XP%GYS% 0  -P0  !D
M             ( !UCD  'AL+W=O<FMS:&5E=',O<VAE970Q-BYX;6Q02P$"
M% ,4    " !&?69/H8-QT:H"   4"P  &0              @ '2.P  >&PO
M=V]R:W-H965T<R]S:&5E=#$W+GAM;%!+ 0(4 Q0    ( $9]9D^KMI0,(P(
M /X&   9              "  ;,^  !X;"]W;W)K<VAE971S+W-H965T,3@N
M>&UL4$L! A0#%     @ 1GUF3Q8 -&S3 0  G 0  !D              ( !
M#4$  'AL+W=O<FMS:&5E=',O<VAE970Q.2YX;6Q02P$"% ,4    " !&?69/
MZ(5"!;<!  #2 P  &0              @ $70P  >&PO=V]R:W-H965T<R]S
M:&5E=#(P+GAM;%!+ 0(4 Q0    ( $9]9D]5#IEWQ $  #<$   9
M      "  05%  !X;"]W;W)K<VAE971S+W-H965T,C$N>&UL4$L! A0#%
M  @ 1GUF3^[RTI(4 @  U08  !D              ( ! $<  'AL+W=O<FMS
M:&5E=',O<VAE970R,BYX;6Q02P$"% ,4    " !&?69/F0%Q5K<!  #2 P
M&0              @ %+20  >&PO=V]R:W-H965T<R]S:&5E=#(S+GAM;%!+
M 0(4 Q0    ( $9]9D\_+R^L5@(  .D'   9              "  3E+  !X
M;"]W;W)K<VAE971S+W-H965T,C0N>&UL4$L! A0#%     @ 1GUF3^[^#'P6
M!   >!0  !D              ( !QDT  'AL+W=O<FMS:&5E=',O<VAE970R
M-2YX;6Q02P$"% ,4    " !&?69/I0XR(K8!  #2 P  &0
M@ $34@  >&PO=V]R:W-H965T<R]S:&5E=#(V+GAM;%!+ 0(4 Q0    ( $9]
M9D]@5[PU% (  *4%   9              "  0!4  !X;"]W;W)K<VAE971S
M+W-H965T,C<N>&UL4$L! A0#%     @ 1GUF3P<H#-K4 0  ;P0  !D
M         ( !2U8  'AL+W=O<FMS:&5E=',O<VAE970R."YX;6Q02P$"% ,4
M    " !&?69/IWHB^U4"  #I!P  &0              @ %66   >&PO=V]R
M:W-H965T<R]S:&5E=#(Y+GAM;%!+ 0(4 Q0    ( $9]9D]8?>+6IP$  +L#
M   9              "  >):  !X;"]W;W)K<VAE971S+W-H965T,S N>&UL
M4$L! A0#%     @ 1GUF3PA#"6[E 0  KP0  !D              ( !P%P
M 'AL+W=O<FMS:&5E=',O<VAE970S,2YX;6Q02P$"% ,4    " !&?69/@Z4Q
MTFH"   E"   &0              @ '<7@  >&PO=V]R:W-H965T<R]S:&5E
M=#,R+GAM;%!+ 0(4 Q0    ( $9]9D^>2_@\3@0    5   9
M  "  7UA  !X;"]W;W)K<VAE971S+W-H965T,S,N>&UL4$L! A0#%     @
M1GUF3R5/19V] 0  T@,  !D              ( ! F8  'AL+W=O<FMS:&5E
M=',O<VAE970S-"YX;6Q02P$"% ,4    " !&?69/1UP:[=H%  !Q(@  &0
M            @ 'V9P  >&PO=V]R:W-H965T<R]S:&5E=#,U+GAM;%!+ 0(4
M Q0    ( $9]9D]]M-*JT0$  #D$   9              "  0=N  !X;"]W
M;W)K<VAE971S+W-H965T,S8N>&UL4$L! A0#%     @ 1GUF3P,<-JY% @
MK0<  !D              ( !#W   'AL+W=O<FMS:&5E=',O<VAE970S-RYX
M;6Q02P$"% ,4    " !&?69/7ZQJ2V<'  #Q+0  &0              @ &+
M<@  >&PO=V]R:W-H965T<R]S:&5E=#,X+GAM;%!+ 0(4 Q0    ( $9]9D\?
MX=_3V ,  $\3   9              "  2EZ  !X;"]W;W)K<VAE971S+W-H
M965T,SDN>&UL4$L! A0#%     @ 1GUF3PO+IS;G!@  =BP  !D
M     ( !.'X  'AL+W=O<FMS:&5E=',O<VAE970T,"YX;6Q02P$"% ,4
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M+GAM;%!+ 0(4 Q0    ( $9]9D^-NCZ]30,  &(.   9              "
M ;R3  !X;"]W;W)K<VAE971S+W-H965T-#4N>&UL4$L! A0#%     @ 1GUF
M3UC\EHEX P  U0\  !D              ( !0)<  'AL+W=O<FMS:&5E=',O
M<VAE970T-BYX;6Q02P$"% ,4    " !&?69/-+'<O'4#   E#P  &0
M        @ 'OF@  >&PO=V]R:W-H965T<R]S:&5E=#0W+GAM;%!+ 0(4 Q0
M   ( $9]9D\(0(S5; (  "H(   9              "  9N>  !X;"]W;W)K
M<VAE971S+W-H965T-#@N>&UL4$L! A0#%     @ 1GUF3[N0"XA@"   _C(
M !D              ( !/J$  'AL+W=O<FMS:&5E=',O<VAE970T.2YX;6Q0
M2P$"% ,4    " !&?69/G[>D]3N8  #FD ( %               @ '5J0
M>&PO<VAA<F5D4W1R:6YG<RYX;6Q02P$"% ,4    " !&?69/4J#=JE,"  "X
M"P  #0              @ %"0@$ >&PO<W1Y;&5S+GAM;%!+ 0(4 Q0    (
M $9]9D_Q9M*'Y ,   0A   /              "  <!$ 0!X;"]W;W)K8F]O
M:RYX;6Q02P$"% ,4    " !&?69/G.$P>-0!   ('@  &@
M@ '12 $ >&PO7W)E;',O=V]R:V)O;VLN>&UL+G)E;'-02P$"% ,4    " !&
M?69/8H^-M<0!  #_'0  $P              @ '=2@$ 6T-O;G1E;G1?5'EP
=97-=+GAM;%!+!08     .@ Z ,@/  #23 $    !

end
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>23
<FILENAME>R40.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6826983360">
<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>Sep. 30, 2019</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 606<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,349<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 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 " 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">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 1 Percent 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 " 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">$ 783,700<span></span>
</td>
<td class="fn" style="border-bottom: 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 " 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">202,904<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 146,281<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_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">606<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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 " 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">2,195,958<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,017,298<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="re">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,296,598<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">1,252,960<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="ro">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">16,600<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">50,200<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="re">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">283,365<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">276,612<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">366,272<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[6]</sup></td>
<td class="nump">260,154<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 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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,200<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">43,265<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">79,942<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="re">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">2,948<span></span>
</td>
<td class="fn" style="border-bottom: 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] | 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="ro">
<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 " 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">202,904<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">146,281<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_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">569,176<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">406,435<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">366,272<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">260,154<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " 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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">1,626,176<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,609,514<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="re">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,296,598<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">1,252,960<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="ro">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">283,365<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">276,612<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="re">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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="ro">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">43,265<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">79,942<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="re">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,948<span></span>
</td>
<td class="fn" style="border-bottom: 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] | 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="ro">
<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 " 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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Investment in ProQR Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">606<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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 " 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">606<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,349<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="7"></td></tr>
<tr><td colspan="7"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in cash and cash equivalents.</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.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">$16.6 million was included in cash and cash equivalents, with the difference included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">$50.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[6]</td>
<td style="vertical-align: top;" valign="top">$3.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[7]</td>
<td style="vertical-align: top;" valign="top">$14.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</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=117815213&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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_AvailableForSaleSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<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 and equity securities categorized neither as held-to-maturity nor trading.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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://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=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=99377092&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=6877327&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_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_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_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>24
<FILENAME>R44.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6667767216">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bayer (Details) - Bayer [Member] - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Oct. 31, 2019</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 175<span></span>
</td>
</tr>
<tr class="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_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MilestonePaymentEarned', window );">Milestone payment earned</a></td>
<td class="nump">$ 10<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_MilestonePaymentEarned">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Milestone payment earned during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MilestonePaymentEarned</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 milestone 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_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>25
<FILENAME>R48.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6803152240">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Pfizer (Details) - Akcea [Member] - USD ($)<br> shares in Millions, $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Oct. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><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>
</tr>
<tr class="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_SublicenseFeePaidForLicenseOfDrug', window );">Sublicense fee paid for license of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75<span></span>
</td>
</tr>
<tr class="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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.8<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Pfizer [Member] | Forecast [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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>
</tr>
<tr class="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_SublicenseFeePaidForLicenseOfDrug', window );">Sublicense fee paid for license of drug</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 125<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Pfizer [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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>
</tr>
<tr class="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_UpfrontLicenseFeeToBeReceived', window );">Upfront license fee to be received</a></td>
<td class="nump">$ 250<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones', window );">Maximum amount of payments receivable for development, regulatory and sales milestones</a></td>
<td class="nump">$ 1,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfDrug', window );">Royalty percentage received on net sales of drug</a></td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_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_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for development, regulatory and sales milestones under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ReceiptOfSharesInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ReceiptOfSharesInSubsidiary</td>
</tr>
<tr>
<td style="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_RoyaltyPercentageReceivedOnNetSalesOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_SublicenseFeePaidForLicenseOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of the sublicense fee paid in common stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_SublicenseFeePaidForLicenseOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_UpfrontLicenseFeeToBeReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 license fees expected to be received 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_UpfrontLicenseFeeToBeReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_StatementScenarioAxis=srt_ScenarioForecastMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_StatementScenarioAxis=srt_ScenarioForecastMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>26
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6993155824">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Noncontrolling Interest in Akcea (Details) - Akcea [Member] - shares<br> shares in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Apr. 30, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NoncontrollingInterestAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">76.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">100.00%<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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Forecast [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NoncontrollingInterestAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="nump">6.9<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>
<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_ReceiptOfSharesInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ReceiptOfSharesInSubsidiary</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NoncontrollingInterestAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_NoncontrollingInterestAbstract</td>
</tr>
<tr>
<td style="padding-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_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_StatementScenarioAxis=srt_ScenarioForecastMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_StatementScenarioAxis=srt_ScenarioForecastMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>27
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6828407216">
<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="2">1 Months Ended</th>
<th class="th" colspan="6">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Feb. 28, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>May 31, 2015 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract', window );">Number of performance obligations at inception of contract | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_MajorCustomersAxis=ions_BiogenIncMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfAgreementsWithCollaborationPartner', window );">Number of agreements | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,082<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 12,746<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 11,638<span></span>
</td>
<td class="nump">$ 14,232<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">2018 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 earned and amortized over period of performance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(16,500)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | IONIS-LRRK2 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember', window );">Alnylam [Member] | Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember', window );">Bayer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember', window );">Bayer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember', window );">Bayer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfAgreementsWithCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of agreements entered into with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfAgreementsWithCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of performance obligations at the inception of a contract.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPriceAdditions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPriceAdditions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_BiogenIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_BiogenIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_IONISLRRK2Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_IONISLRRK2Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>28
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6637549920">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Operating Leases (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LeasesAbstract', window );"><strong>Operating 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_LesseeOperatingLeaseInformationTableTextBlock', window );">Amounts Related to Operating Leases</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>

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

<table cellpadding="0" cellspacing="0" id="zf42106fcdfa447c3a605f18b4bb6c5cc" 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: center;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">At September 30, 2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom">&#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: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z134ddf538270485d8e34269956271e23" 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 deposits and other assets on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb6759401030e41a8ab46de882c820315" 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;">Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock', window );">Future Minimum Payments Under Operating Leases</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2019, the payments for our operating lease liabilities are as follows (in thousands):</div>

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

<table cellpadding="0" cellspacing="0" id="zb029d562d7d14830957cb4fe63551490" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Remainder of 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">801</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Years ending December 31,</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,282</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,781</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,520</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,264</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imputed interest</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,533</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating lease liabilities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,731</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseInformationTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseInformationTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LeasesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_LeasesAbstract</td>
</tr>
<tr>
<td style="padding-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_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 future minimum lease payments as of the date of the latest balance sheet presented, in aggregate and for each of the five years succeeding fiscal years, with separate deductions from the total for the amount representing executor costs, including any profit thereon, included in the minimum lease payments and for the amount of the imputed interest necessary to reduce the net minimum lease payments to present 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/otherTransitionRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 840<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=84164817&amp;loc=d3e45280-112737<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>JSON
<SEQUENCE>29
<FILENAME>MetaLinks.json
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
{
 "instance": {
  "form10q.htm": {
   "axisCustom": 0,
   "axisStandard": 27,
   "contextCount": 392,
   "dts": {
    "calculationLink": {
     "local": [
      "ions-20190930_cal.xml"
     ]
    },
    "definitionLink": {
     "local": [
      "ions-20190930_def.xml"
     ],
     "remote": [
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-eedm-def-2019-01-31.xml",
      "http://xbrl.fasb.org/srt/2019/elts/srt-eedm1-def-2019-01-31.xml"
     ]
    },
    "inline": {
     "local": [
      "form10q.htm"
     ]
    },
    "labelLink": {
     "local": [
      "ions-20190930_lab.xml"
     ],
     "remote": [
      "https://xbrl.sec.gov/dei/2019/dei-doc-2019-01-31.xml",
      "https://xbrl.sec.gov/invest/2013/invest-doc-2013-01-31.xml",
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-doc-2019-01-31.xml"
     ]
    },
    "presentationLink": {
     "local": [
      "ions-20190930_pre.xml"
     ]
    },
    "referenceLink": {
     "remote": [
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-ref-2019-01-31.xml",
      "https://xbrl.sec.gov/dei/2019/dei-ref-2019-01-31.xml",
      "https://xbrl.sec.gov/invest/2013/invest-ref-2013-01-31.xml"
     ]
    },
    "schema": {
     "local": [
      "ions-20190930.xsd"
     ],
     "remote": [
      "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/lrr/role/net-2009-12-16.xsd",
      "http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd",
      "https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd",
      "http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd",
      "http://www.xbrl.org/2005/xbrldt-2005.xsd",
      "http://www.xbrl.org/dtr/type/nonNumeric-2009-12-16.xsd",
      "http://www.xbrl.org/dtr/type/numeric-2009-12-16.xsd",
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-gaap-2019-01-31.xsd",
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-roles-2019-01-31.xsd",
      "http://xbrl.fasb.org/srt/2019/elts/srt-2019-01-31.xsd",
      "http://www.xbrl.org/2006/ref-2006-02-27.xsd",
      "http://xbrl.fasb.org/srt/2019/elts/srt-types-2019-01-31.xsd",
      "http://xbrl.fasb.org/srt/2019/elts/srt-roles-2019-01-31.xsd",
      "https://xbrl.sec.gov/country/2017/country-2017-01-31.xsd",
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-types-2019-01-31.xsd",
      "https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd",
      "https://xbrl.sec.gov/currency/2019/currency-2019-01-31.xsd",
      "https://xbrl.sec.gov/exch/2019/exch-2019-01-31.xsd",
      "https://xbrl.sec.gov/naics/2017/naics-2017-01-31.xsd",
      "https://xbrl.sec.gov/sic/2011/sic-2011-01-31.xsd",
      "https://xbrl.sec.gov/stpr/2018/stpr-2018-01-31.xsd",
      "http://www.xbrl.org/2004/ref-2004-08-10.xsd",
      "http://www.xbrl.org/lrr/arcrole/factExplanatory-2009-12-16.xsd",
      "http://www.xbrl.org/lrr/role/reference-2009-12-16.xsd",
      "http://xbrl.fasb.org/us-gaap/2019/elts/us-parts-codification-2019-01-31.xsd",
      "http://www.xbrl.org/lrr/role/deprecated-2009-12-16.xsd"
     ]
    }
   },
   "elementCount": 493,
   "entityCount": 1,
   "hidden": {
    "http://isispharm.com/20190930": 1,
    "http://xbrl.sec.gov/dei/2019-01-31": 6,
    "total": 7
   },
   "keyCustom": 55,
   "keyStandard": 293,
   "memberCustom": 37,
   "memberStandard": 33,
   "nsprefix": "ions",
   "nsuri": "http://isispharm.com/20190930",
   "report": {
    "R1": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "dei:EntityCurrentReportingStatus",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "document",
     "isDefault": "true",
     "longName": "000100 - Document - Document and Entity Information",
     "role": "http://isispharm.com/role/DocumentAndEntityInformation",
     "shortName": "Document and Entity Information",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "dei:EntityCurrentReportingStatus",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R10": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "invest:InvestmentTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060300 - Disclosure - Investments",
     "role": "http://isispharm.com/role/Investments",
     "shortName": "Investments",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "invest:InvestmentTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R11": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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://isispharm.com/role/FairValueMeasurements",
     "shortName": "Fair Value Measurements",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:LesseeOperatingLeasesTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060500 - Disclosure - Operating Leases",
     "role": "http://isispharm.com/role/OperatingLeases",
     "shortName": "Operating Leases",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:LesseeOperatingLeasesTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R13": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:IncomeTaxDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060600 - Disclosure - Income Taxes",
     "role": "http://isispharm.com/role/IncomeTaxes",
     "shortName": "Income Taxes",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:IncomeTaxDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R14": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:CollaborativeArrangementDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060700 - Disclosure - Collaborative Arrangements and Licensing Agreements",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements",
     "shortName": "Collaborative Arrangements and Licensing Agreements",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:CollaborativeArrangementDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R15": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SegmentReportingDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060800 - Disclosure - Segment Information",
     "role": "http://isispharm.com/role/SegmentInformation",
     "shortName": "Segment Information",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SegmentReportingDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R16": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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://isispharm.com/role/BasisOfPresentationPolicies",
     "shortName": "Basis of Presentation (Policies)",
     "subGroupType": "policies",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:BasisOfAccountingPolicyPolicyTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R17": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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://isispharm.com/role/SignificantAccountingPoliciesPolicies",
     "shortName": "Significant Accounting Policies (Policies)",
     "subGroupType": "policies",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:RevenueFromContractWithCustomerPolicyTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R18": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080200 - Disclosure - Significant Accounting Policies (Tables)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesTables",
     "shortName": "Significant Accounting Policies (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R19": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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://isispharm.com/role/InvestmentsTables",
     "shortName": "Investments (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R2": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "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 (Unaudited)",
     "role": "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited",
     "shortName": "CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited)",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "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": "c20190101to20190930",
      "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://isispharm.com/role/FairValueMeasurementsTables",
     "shortName": "Fair Value Measurements (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R21": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "ions:LesseeOperatingLeaseInformationTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080500 - Disclosure - Operating Leases (Tables)",
     "role": "http://isispharm.com/role/OperatingLeasesTables",
     "shortName": "Operating Leases (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "ions:LesseeOperatingLeaseInformationTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R22": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080700 - Disclosure - Collaborative Arrangements and Licensing Agreements (Tables)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables",
     "shortName": "Collaborative Arrangements and Licensing Agreements (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R23": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080800 - Disclosure - Segment Information (Tables)",
     "role": "http://isispharm.com/role/SegmentInformationTables",
     "shortName": "Segment Information (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R24": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190331_OwnershipAxis_AkceaTherapeuticsIncMember",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "us-gaap:MinorityInterestOwnershipPercentageByParent",
      "reportCount": 1,
      "unitRef": "U003",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090100 - Disclosure - Basis of Presentation (Details)",
     "role": "http://isispharm.com/role/BasisOfPresentationDetails",
     "shortName": "Basis of Presentation (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R25": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U005",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090200 - Disclosure - Significant Accounting Policies, Revenue Recognition (Details)",
     "role": "http://isispharm.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": "c20190101to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U005",
      "xsiNil": "false"
     }
    },
    "R26": {
     "firstAnchor": null,
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090202 - Disclosure - Significant Accounting Policies, Contracts Receivable (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails",
     "shortName": "Significant Accounting Policies, Contracts Receivable (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R27": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "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://isispharm.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": "c20190701to20190930",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "us-gaap:ContractWithCustomerLiabilityRevenueRecognized",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R28": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "ions:CostOfProductsSoldPreviouslyRecognized",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090206 - Disclosure - Significant Accounting Policies, Cost of Products Sold (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails",
     "shortName": "Significant Accounting Policies, Cost of Products Sold (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "ions:CostOfProductsSoldPreviouslyRecognized",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R29": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190331_OwnershipAxis_AkceaTherapeuticsIncMember",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "us-gaap:MinorityInterestOwnershipPercentageByParent",
      "reportCount": 1,
      "unitRef": "U003",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090208 - Disclosure - Significant Accounting Policies, Noncontrolling Interest in Akcea (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails",
     "shortName": "Significant Accounting Policies, Noncontrolling Interest in Akcea (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R3": {
     "firstAnchor": {
      "ancestors": [
       "us-gaap:CommonStockParOrStatedValuePerShare",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "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 (Unaudited) (Parenthetical)",
     "role": "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
     "shortName": "CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) (Parenthetical)",
     "subGroupType": "parenthetical",
     "uniqueAnchor": {
      "ancestors": [
       "us-gaap:CommonStockParOrStatedValuePerShare",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "3",
      "first": true,
      "lang": null,
      "name": "us-gaap:CommonStockParOrStatedValuePerShare",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U004",
      "xsiNil": "false"
     }
    },
    "R30": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment",
      "reportCount": 1,
      "unitRef": "U007",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090210 - Disclosure - Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails",
     "shortName": "Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R31": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:InventoryWriteDown",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090212 - Disclosure - Significant Accounting Policies, Inventory Valuation (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails",
     "shortName": "Significant Accounting Policies, Inventory Valuation (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:InventoryWriteDown",
      "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": "c20190930",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "us-gaap:OperatingLeaseRightOfUseAsset",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090214 - Disclosure - Significant Accounting Policies, Leases (Details)",
     "role": "http://isispharm.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": "c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:OperatingLeaseRightOfUseAsset",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R33": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "us-gaap:EarningsPerShareBasic",
      "reportCount": 1,
      "unitRef": "U004",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090216 - Disclosure - Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
     "shortName": "Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "lang": null,
      "name": "us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R34": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "us-gaap:NumberOfOperatingSegments",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U008",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090218 - Disclosure - Significant Accounting Policies, Segment Information (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails",
     "shortName": "Significant Accounting Policies, Segment Information (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "us-gaap:NumberOfOperatingSegments",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U008",
      "xsiNil": "false"
     }
    },
    "R35": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfExecutiveOfficersTerminatingEmployment",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U009",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090220 - Disclosure - Significant Accounting Policies, Stock-Based Compensation Expense (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails",
     "shortName": "Significant Accounting Policies, Stock-Based Compensation Expense (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfExecutiveOfficersTerminatingEmployment",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U009",
      "xsiNil": "false"
     }
    },
    "R36": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "-6",
      "first": true,
      "lang": null,
      "name": "us-gaap:StockRepurchaseProgramAuthorizedAmount1",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090222 - Disclosure - Significant Accounting Policies, Share Repurchase Program (Details)",
     "role": "http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails",
     "shortName": "Significant Accounting Policies, Share Repurchase Program (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "-6",
      "first": true,
      "lang": null,
      "name": "us-gaap:StockRepurchaseProgramAuthorizedAmount1",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R37": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "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://isispharm.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": "c20190930",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U003",
      "xsiNil": "false"
     }
    },
    "R38": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:EquitySecuritiesFvNiCost",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090302 - Disclosure - Investments, Summary of Investments (Details)",
     "role": "http://isispharm.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": "c20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:EquitySecuritiesFvNiCost",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R39": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "0",
      "first": true,
      "lang": null,
      "name": "us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U010",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090304 - Disclosure - Investments, Investments Temporarily Impaired (Details)",
     "role": "http://isispharm.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": "c20190930",
      "decimals": "0",
      "first": true,
      "lang": null,
      "name": "us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U010",
      "xsiNil": "false"
     }
    },
    "R4": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "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 (Unaudited)",
     "role": "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited)",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "lang": null,
      "name": "us-gaap:CostOfGoodsAndServicesSold",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R40": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:EquitySecuritiesFvNi",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090400 - Disclosure - Fair Value Measurements (Details)",
     "role": "http://isispharm.com/role/FairValueMeasurementsDetails",
     "shortName": "Fair Value Measurements (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:NotesPayableFairValueDisclosure",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R41": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "us-gaap:OperatingLeaseRightOfUseAsset",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090500 - Disclosure - Operating Leases (Details)",
     "role": "http://isispharm.com/role/OperatingLeasesDetails",
     "shortName": "Operating Leases (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:OperatingLeasePayments",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R42": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:IncomeTaxExpenseBenefit",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090600 - Disclosure - Income Taxes (Details)",
     "role": "http://isispharm.com/role/IncomeTaxesDetails",
     "shortName": "Income Taxes (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R43": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090700 - Disclosure - Collaborative Arrangements and Licensing Agreements, Biogen (Details)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements, Biogen (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R44": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember",
      "decimals": "-6",
      "first": true,
      "lang": null,
      "name": "ions:CumulativePaymentsReceived",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090706 - Disclosure - Collaborative Arrangements and Licensing Agreements, Bayer (Details)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements, Bayer (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember",
      "decimals": "-6",
      "first": true,
      "lang": null,
      "name": "ions:CumulativePaymentsReceived",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R45": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090708 - Disclosure - Collaborative Arrangements and Licensing Agreements, GSK (Details)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements, GSK (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember",
      "decimals": "-6",
      "lang": null,
      "name": "us-gaap:ContractWithCustomerLiability",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R46": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090710 - Disclosure - Collaborative Arrangements and Licensing Agreements, Roche (Details)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements, Roche (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:ContractWithCustomerLiability",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R47": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090712 - Disclosure - Collaborative Arrangements and Licensing Agreements, Novartis (Details)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements, Novartis (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:ContractWithCustomerLiability",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R48": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember",
      "decimals": "-6",
      "first": true,
      "lang": null,
      "name": "ions:SublicenseFeePaidForLicenseOfDrug",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090716 - Disclosure - Collaborative Arrangements and Licensing Agreements, Pfizer (Details)",
     "role": "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements, Pfizer (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember",
      "decimals": "-6",
      "lang": null,
      "name": "ions:SublicenseFeePaidForLicenseOfDrug",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R49": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "us-gaap:NumberOfReportableSegments",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U008",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090800 - Disclosure - Segment Information (Details)",
     "role": "http://isispharm.com/role/SegmentInformationDetails",
     "shortName": "Segment Information (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "us-gaap:NumberOfReportableSegments",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U008",
      "xsiNil": "false"
     }
    },
    "R5": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:ProfitLoss",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "030000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Unaudited)",
     "role": "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Unaudited)",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190701to20190930",
      "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": "c20171231_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 (Unaudited)",
     "role": "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited)",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20171231_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": "c20190101to20190930",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:ProfitLoss",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "050000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited)",
     "role": "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited)",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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": "c20190101to20190930",
      "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://isispharm.com/role/BasisOfPresentation",
     "shortName": "Basis of Presentation",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "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": "c20190101to20190930",
      "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://isispharm.com/role/SignificantAccountingPolicies",
     "shortName": "Significant Accounting Policies",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20190101to20190930",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SignificantAccountingPoliciesTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    }
   },
   "segmentCount": 77,
   "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "fiscalPeriodItemType"
    },
    "dei_DocumentFiscalYearFocus": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "This is focus fiscal year of the document report in CCYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.",
        "label": "Document Fiscal Year Focus"
       }
      }
     },
     "localname": "DocumentFiscalYearFocus",
     "nsuri": "http://xbrl.sec.gov/dei/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "gYearItemType"
    },
    "dei_DocumentPeriodEndDate": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The end date of the period reflected on the cover page if a periodic report. For all other reports and registration statements containing historical data, it is the date up through which that historical data is presented.  If there is no historical data in the report, use the filing date. The format of the date is CCYY-MM-DD.",
        "label": "Document Period End Date"
       }
      }
     },
     "localname": "DocumentPeriodEndDate",
     "nsuri": "http://xbrl.sec.gov/dei/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "dateItemType"
    },
    "dei_DocumentQuarterlyReport": {
     "auth_ref": [
      "r365"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_DocumentTransitionReport": {
     "auth_ref": [
      "r366"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "stateOrProvinceItemType"
    },
    "dei_EntityCentralIndexKey": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "yesNoItemType"
    },
    "dei_EntityEmergingGrowthCompany": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "fileNumberItemType"
    },
    "dei_EntityFilerCategory": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "edgarStateCountryItemType"
    },
    "dei_EntityInteractiveDataCurrent": {
     "auth_ref": [
      "r368"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "yesNoItemType"
    },
    "dei_EntityRegistrantName": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_EntityShellCompany": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_EntitySmallBusiness": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_EntityTaxIdentificationNumber": {
     "auth_ref": [
      "r367"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_Security12bTitle": {
     "auth_ref": [
      "r363"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "securityTitleItemType"
    },
    "dei_SecurityExchangeName": {
     "auth_ref": [
      "r364"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "tradingSymbolItemType"
    },
    "invest_InvestmentTextBlock": {
     "auth_ref": [
      "r369"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The entire disclosure for investments, including all tables.",
        "label": "Investments"
       }
      }
     },
     "localname": "InvestmentTextBlock",
     "nsuri": "http://xbrl.sec.gov/invest/2013-01-31",
     "presentation": [
      "http://isispharm.com/role/Investments"
     ],
     "xbrltype": "textBlockItemType"
    },
    "invest_InvestmentsScheduleAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Investments Schedule [Abstract]",
        "terseLabel": "Ownership Interests in Private and Public Companies [Abstract]"
       }
      }
     },
     "localname": "InvestmentsScheduleAbstract",
     "nsuri": "http://xbrl.sec.gov/invest/2013-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_AKCEAAPOALMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "An antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein Lp(a).",
        "label": "AKCEA-APO(a)-L [Member]",
        "terseLabel": "AKCEA-APO(a)-L [Member]"
       }
      }
     },
     "localname": "AKCEAAPOALMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_AkceaTherapeuticsIncMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Akcea Therapeutics, Inc. is a subsidiary of the Company and was formed to develop and commercialize drugs for cardiometabolic disorders.",
        "label": "Akcea Therapeutics, Inc. [Member]",
        "terseLabel": "Akcea [Member]"
       }
      }
     },
     "localname": "AkceaTherapeuticsIncMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_AkceaTherapeuticsMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Reportable segment which includes the operations of the Company's wholly-owned subsidiary, Akcea Therapeutics, Inc., which was formed to develop and commercialize drugs for cardiometabolic disorders.",
        "label": "Akcea Therapeutics [Member]",
        "terseLabel": "Akcea Therapeutics [Member]"
       }
      }
     },
     "localname": "AkceaTherapeuticsMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.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 years of the balance sheet date.",
        "label": "Available-for-sale Securities, Debt Maturities, after Two Through Three Years, Percentage",
        "terseLabel": "After two years but within three years"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BoardOfDirectorStockOptionMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "An arrangement whereby a member of the Board of Directors is entitled to receive in the future, subject to vesting and other restrictions, a number of shares in the entity at a specified price, as defined in the agreement, as a form of compensation.",
        "label": "Board of Director Stock Option [Member]",
        "terseLabel": "Board of Director Stock Options [Member]"
       }
      }
     },
     "localname": "BoardOfDirectorStockOptionMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BoardOfDirectorsMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "A group of individuals that are elected as, or elected to act as, representatives of the stockholders to establish corporate management related policies and to make decisions on major company issues.",
        "label": "Board of Directors [Member]"
       }
      }
     },
     "localname": "BoardOfDirectorsMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CashCashEquivalentsAndInvestmentsPolicyTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Disclosure of accounting policy for cash, cash equivalents and investments.",
        "label": "Cash, Cash Equivalents and Investments [Policy Text Block]",
        "terseLabel": "Cash, Cash Equivalents and Investments"
       }
      }
     },
     "localname": "CashCashEquivalentsAndInvestmentsPolicyTextBlock",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Collaborative Arrangement and Licensing Agreement [Abstract]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementAbstract",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to collaborative arrangement with Bayer HealthCare amended in February 2017 to advance IONIS-FXIRx for the prevention of thrombosis and to initiate development of IONIS-FXI-LRx.",
        "label": "Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]",
        "terseLabel": "Bayer [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in April 2013 to develop treatments for Huntington's disease, or HD, based on the Company's antisense technology.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in April 2013 with Roche [Member]",
        "terseLabel": "Huntington's Disease [Member]",
        "verboseLabel": "Roche [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the expanded collaborative arrangement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in April 2018 with Biogen [Member]",
        "terseLabel": "2018 Strategic Neurology [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2012. This agreement is focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases (Neurology).",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in December 2012 with Biogen [Member]",
        "terseLabel": "2012 Neurology [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in December 2017 with Biogen [Member]",
        "terseLabel": "New Antisense Medicines for the Treatment of SMA [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2017WithBiogenMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Novartis to develop and commercialize AKCEA-APO(a)-L and AKCEA-APOCIII-L.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in January 2017 with Novartis [Member]",
        "terseLabel": "Novartis [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in March 2004 with Alnylam Pharmaceuticals, Inc. [Member]",
        "terseLabel": "Alnylam [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement and licensing agreement entered into with GlaxoSmithKline (GSK) in March 2010 to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in March 2010 with GSK [Member]",
        "terseLabel": "GSK [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to collaborative arrangement entered into with Bayer HealthCare in May 2015 to develop and commercialize IONIS-FXI for the prevention of thrombosis.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in May 2015 with Bayer [Member]",
        "terseLabel": "Bayer [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-LRx for the treatment of complement-mediated diseases.",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in October 2018 with Roche [Member]",
        "terseLabel": "IONIS-FB-L for Complement-Mediated Diseases [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Pfizer for the license of AKCEA-ANGPTL3-LR to treat people with cardiovascular and metabolic diseases..",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in October 2019 with Pfizer [Member]",
        "terseLabel": "Pfizer [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangement entered into with Biogen Inc. in September 2013. This agreement is a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases (Strategic Neurology).",
        "label": "Collaborative Arrangement and Licensing Agreement Entered Into in September 2013 with Biogen [Member]",
        "terseLabel": "2013 Strategic Neurology [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementsAndLicensingAgreementsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Collaborative Arrangements and Licensing Agreements [Abstract]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndLicensingAgreementsAbstract",
     "nsuri": "http://isispharm.com/20190930",
     "xbrltype": "stringItemType"
    },
    "ions_CollaborativeArrangementsAndLicensingAgreementsBayerMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Bayer HealthCare.",
        "label": "Collaborative Arrangements and Licensing Agreements, Bayer [Member]",
        "terseLabel": "Bayer [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndLicensingAgreementsBayerMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Biogen Inc.",
        "label": "Collaborative Arrangements and Licensing Agreements, Biogen [Member]",
        "terseLabel": "Biogen [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndLicensingAgreementsBiogenMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents information pertaining to the collaborative arrangements and licensing agreements entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche.",
        "label": "Collaborative Arrangements and Licensing Agreements, Roche [Member]",
        "terseLabel": "Roche [Member]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndLicensingAgreementsRocheMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems": {
     "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 Disclosure [Line Items]",
        "terseLabel": "Collaborative Arrangements and Licensing Agreements [Abstract]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Disclosure of information about collaborative arrangements and non-collaborative arrangement transactions.",
        "label": "Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Table]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_CommercialMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Commercial [Member]",
        "terseLabel": "Commercial Revenue [Member]"
       }
      }
     },
     "localname": "CommercialMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "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 Percent Notes [Member]"
       }
      }
     },
     "localname": "ConvertibleSeniorNotes1PercentMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CostOfProductsSoldPreviouslyRecognized": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The costs related to goods produced and sold that were previously recognized as expense and are related to the commercial revenue recognized during the period.",
        "label": "Cost of Products Sold Previously Recognized",
        "terseLabel": "Previously expensed costs to produce TEGSEDI related to TEGSEDI commercial revenue"
       }
      }
     },
     "localname": "CostOfProductsSoldPreviouslyRecognized",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi": {
     "auth_ref": [],
     "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost": {
     "auth_ref": [],
     "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",
        "terseLabel": "Cost"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain": {
     "auth_ref": [],
     "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss": {
     "auth_ref": [],
     "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_EmployeeMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Persons hired to provide services to a company on a regular basis in exchange for compensation.",
        "label": "Employee [Member]",
        "terseLabel": "Employees [Member]"
       }
      }
     },
     "localname": "EmployeeMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_EquityIncentivePlan2011Member": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Represents the stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to employees, directors, and consultants.",
        "label": "Equity Incentive Plan 2011 [Member]",
        "terseLabel": "2011 Equity Incentive Plan [Member]"
       }
      }
     },
     "localname": "EquityIncentivePlan2011Member",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_IONISLRRK2Member": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "ONIS-LRRK2Rx (BIIB094) is an antisense drug for the treatment of people with Parkinson's disease.",
        "label": "IONIS-LRRK2 [Member]",
        "terseLabel": "IONIS-LRRK2 [Member]"
       }
      }
     },
     "localname": "IONISLRRK2Member",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_IONISMAPTMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "IONIS-MAPT is an antisense drug designed to selectively reduce the production of microtubule-associated protein tau (MAPT), or tau protein, in the brain, for the treatment of Alzheimer's disease.",
        "label": "IONIS-MAPT [Member]",
        "terseLabel": "IONIS-MAPT [Member]"
       }
      }
     },
     "localname": "IONISMAPTMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_IncreaseDecreaseInAccruedAndDeferredLiabilities": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 20.0,
       "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 expenses incurred but not yet paid and deferred liabilities due within one year or operating cycle.",
        "label": "Increase (Decrease) in Accrued and Deferred Liabilities",
        "terseLabel": "Accrued liabilities and deferred rent"
       }
      }
     },
     "localname": "IncreaseDecreaseInAccruedAndDeferredLiabilities",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails": {
       "order": 2.0,
       "parentTag": "us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding",
       "weight": 1.0
      }
     },
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.",
        "label": "Incremental Common Shares Attributable to Employee Stock Purchase Plan",
        "verboseLabel": "Shares issuable related to our Employee Stock Purchase Plan (in shares)"
       }
      }
     },
     "localname": "IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "ions_IonisCoreMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Reportable segment in which the Company is exploiting a novel drug discovery platform created to generate a broad pipeline of first-in-class or best-in-class drugs for the Company and its partners. This segment generates revenue from a multifaceted partnering strategy. This strategy includes revenue from collaborations with preferred partners, traditional alliances and working with a consortium of companies that can exploit the Company's drugs and technology. Revenue from collaborations with preferred partners and traditional alliances may consist of upfront payments, milestone payments, licensing fees and royalties.",
        "label": "Ionis Core [Member]",
        "terseLabel": "Ionis [Member]",
        "verboseLabel": "Ionis Core [Member]"
       }
      }
     },
     "localname": "IonisCoreMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_IonisHttMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "An antisense drug targeting huntingtin, or HTT, protein.",
        "label": "IONIS-HTT [Member]",
        "terseLabel": "IONIS-HTT [Member]"
       }
      }
     },
     "localname": "IonisHttMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of options to extend the lease under the lessee's operating leasing arrangement.",
        "label": "Lessee, Leasing Arrangements, Operating Leases, Number of options to extend lease",
        "terseLabel": "Number of options to extend lease"
       }
      }
     },
     "localname": "LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_LesseeOperatingLeaseAllowanceForTenantImprovements": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Allowance for tenant improvements to the office space included in the lessee's operating lease.",
        "label": "Lessee, Operating Lease, Allowance for Tenant Improvements",
        "terseLabel": "Tenant improvement allowance"
       }
      }
     },
     "localname": "LesseeOperatingLeaseAllowanceForTenantImprovements",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_LesseeOperatingLeaseInformationTableTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Tabular disclosure of information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.",
        "label": "Lessee, Operating Lease Information [Table Text Block]",
        "terseLabel": "Amounts Related to Operating Leases"
       }
      }
     },
     "localname": "LesseeOperatingLeaseInformationTableTextBlock",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.",
        "label": "Lessee, Operating Lease, Initial Letter of Credit to Secure Lease Obligation",
        "terseLabel": "Initial amount of letter of credit"
       }
      }
     },
     "localname": "LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the fifth anniversary of the rent commencement date.",
        "label": "Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Fifth Anniversary of Rent Commencement Date",
        "terseLabel": "Letter of credit on fifth anniversary of rent commencement date"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.",
        "label": "Lessee, Operating Lease, Letter of Credit to Secure Lease Obligation on Third Anniversary of Rent Commencement Date",
        "terseLabel": "Letter of credit on third anniversary of rent commencement date"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_LesseeOperatingLeasePeriodOfFreeRent": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.",
        "label": "Lessee, Operating Lease, Period of Free Rent",
        "terseLabel": "Period of free rent under lease"
       }
      }
     },
     "localname": "LesseeOperatingLeasePeriodOfFreeRent",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "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]",
        "terseLabel": "Licensing and Other Royalties [Member]",
        "verboseLabel": "Licensing and Other Royalty Revenue [Member]"
       }
      }
     },
     "localname": "LicensingAndOtherRoyaltiesMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_LongTermObligationsNoncurrent": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 4.0,
       "parentTag": "us-gaap_Liabilities",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of long-term debt and lease obligation, classified as noncurrent.",
        "label": "Long-term Obligations, Noncurrent",
        "terseLabel": "Long-term obligations, less current portion"
       }
      }
     },
     "localname": "LongTermObligationsNoncurrent",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The maximum amount of payments receivable for development, regulatory and sales milestones under the collaboration agreement.",
        "label": "Maximum amount of payments receivable for development, regulatory and sales milestones",
        "terseLabel": "Maximum amount of payments receivable for development, regulatory and sales milestones"
       }
      }
     },
     "localname": "MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_MilestonePaymentEarned": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Milestone payment earned during the period.",
        "label": "Milestone payment earned"
       }
      }
     },
     "localname": "MilestonePaymentEarned",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_MilestonePaymentsReceived": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The amount of milestone payments received during the period under the collaboration agreement.",
        "label": "Milestone payments received",
        "verboseLabel": "Milestone payment received"
       }
      }
     },
     "localname": "MilestonePaymentsReceived",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_NextPotentialMilestonePayment": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The next potential milestone payment to be earned under the collaboration agreement.",
        "label": "Next potential milestone payment",
        "terseLabel": "Next prospective milestone"
       }
      }
     },
     "localname": "NextPotentialMilestonePayment",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_NovartisInternationalAGMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Novartis International AG is a Swiss multinational pharmaceutical company based in Basel, Switzerland.",
        "label": "Novartis International AG [Member]",
        "terseLabel": "Novartis [Member]"
       }
      }
     },
     "localname": "NovartisInternationalAGMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "domainItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfCollaborationAgreements": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of collaboration agreements with the collaboration partner.",
        "label": "Number of collaboration agreements",
        "terseLabel": "Number of collaboration agreements"
       }
      }
     },
     "localname": "NumberOfCollaborationAgreements",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfDrugsCurrentlyBeingAdvanced": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of drugs currently being advanced under the collaboration agreement.",
        "label": "Number of drugs currently being advanced",
        "verboseLabel": "Number of drugs being advanced"
       }
      }
     },
     "localname": "NumberOfDrugsCurrentlyBeingAdvanced",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfExecutiveOfficersTerminatingEmployment": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of executive officers terminating employment with the company.",
        "label": "Number of executive officers terminating employment"
       }
      }
     },
     "localname": "NumberOfExecutiveOfficersTerminatingEmployment",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of medicines currently in development under collaborations.",
        "label": "Number of medicines currently in development under collaborations",
        "terseLabel": "Number of medicines currently in development under collaborations"
       }
      }
     },
     "localname": "NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfMilestonePaymentsAchieved": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of milestone payments achieved during the period under the collaboration agreement.",
        "label": "Number of milestone payments achieved",
        "terseLabel": "Number of milestone payments achieved"
       }
      }
     },
     "localname": "NumberOfMilestonePaymentsAchieved",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfNewTargetsAdvanced": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of new targets advanced during the period under the collaboration agreement.",
        "label": "Number of new targets advanced",
        "terseLabel": "Number of new targets advanced"
       }
      }
     },
     "localname": "NumberOfNewTargetsAdvanced",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "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%"
       }
      }
     },
     "localname": "NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails",
      "http://isispharm.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%"
       }
      }
     },
     "localname": "NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Office and laboratory space in a facility adjacent to the Company's manufacturing facility leased under non-cancelable operating leases.",
        "label": "Office and Laboratory Space Adjacent to Manufacturing Facility [Member]",
        "terseLabel": "Office and Laboratory Space Adjacent to Manufacturing Facility [Member]"
       }
      }
     },
     "localname": "OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_OfficeSpaceForCorporateHeadquartersMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Office space located in Boston, Massachusetts for Akcea Therapeutics, Inc.'s corporate headquarters leased under non-cancelable operating leases.",
        "label": "Office Space for Corporate Headquarters [Member]"
       }
      }
     },
     "localname": "OfficeSpaceForCorporateHeadquartersMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Office space subleased to Akcea Therapeutics, Inc. (Akcea) leased under non-cancelable operating leases.",
        "label": "Office Space Subleased to Akcea Therapeutics, Inc. [Member]",
        "terseLabel": "Office Space Subleased to Akcea [Member]"
       }
      }
     },
     "localname": "OfficeSpaceSubleasedToAkceaTherapeuticsIncMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_OperatingLeaseRightOfUseAssetAmortization": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 2.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of amortization expense attributable to right-of-use asset from operating lease.",
        "label": "Operating Lease, Right-of-Use Asset, Amortization",
        "terseLabel": "Amortization of right-of-use operating lease assets"
       }
      }
     },
     "localname": "OperatingLeaseRightOfUseAssetAmortization",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_PaymentsIncludedInTransactionPriceForPerformanceObligation": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Total payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.",
        "label": "Payments included in transaction price for performance obligation",
        "terseLabel": "Payments included in transaction price for performance obligation"
       }
      }
     },
     "localname": "PaymentsIncludedInTransactionPriceForPerformanceObligation",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_PaymentsToAcquireLicensesAndOtherAssets": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 5.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInInvestingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The cash outflow for acquisition of licenses and other assets not otherwise defined in the taxonomy.",
        "label": "Payments to Acquire Licenses and Other Assets",
        "negatedLabel": "Acquisition of licenses and other assets, net"
       }
      }
     },
     "localname": "PaymentsToAcquireLicensesAndOtherAssets",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_ReceiptOfSharesInSubsidiary": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of shares received from the subsidiary during the period.",
        "label": "Receipt of shares in subsidiary",
        "verboseLabel": "Additional shares of Akcea stock received (in shares)"
       }
      }
     },
     "localname": "ReceiptOfSharesInSubsidiary",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Revenue from research and development services performed under a collaboration agreement.",
        "label": "Research and Development Revenue Under Collaborative Agreements [Member]",
        "terseLabel": "R&amp;D Revenue [Member]",
        "verboseLabel": "R&amp;D Revenue Under Collaborative Agreements [Member]"
       }
      }
     },
     "localname": "ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ResearchAndDevelopmentServicesMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Research and development services performed under a collaboration agreement.",
        "label": "Research and Development Services [Member]",
        "terseLabel": "R&amp;D Services [Member]"
       }
      }
     },
     "localname": "ResearchAndDevelopmentServicesMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ResearchDevelopmentAndPatentExpense": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_ResearchDevelopmentAndPatentMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Primary financial statement caption encompassing research, development and patent expenses.",
        "label": "Research, Development and Patent [Member]",
        "terseLabel": "Research, Development and Patent [Member]"
       }
      }
     },
     "localname": "ResearchDevelopmentAndPatentMember",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The number of performance obligations at the inception of a contract.",
        "label": "Revenue from Contract with Customer, Number of performance obligations at inception of contract",
        "terseLabel": "Number of performance obligations at inception of contract"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.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 earned and amortized over period of performance"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerTransactionPriceAdditions",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_RoyaltyPercentageReceivedOnNetSalesOfDrug": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Royalty percentage received on the net sales of a drug by a collaboration partner under the collaboration agreement.",
        "label": "Royalty percentage received on net sales of drug",
        "terseLabel": "Royalty percentage received on net sales of drug"
       }
      }
     },
     "localname": "RoyaltyPercentageReceivedOnNetSalesOfDrug",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ShareBasedCompensationLineItems": {
     "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 [Line Items]",
        "verboseLabel": "Significant Accounting Policies [Abstract]"
       }
      }
     },
     "localname": "ShareBasedCompensationLineItems",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_ShareBasedCompensationTable": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Disclosure of information about share-based compensation.",
        "label": "Share-based Compensation [Table]"
       }
      }
     },
     "localname": "ShareBasedCompensationTable",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_SublicenseFeePaidForLicenseOfDrug": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The amount of the sublicense fee paid in common stock.",
        "label": "Sublicense fee paid for license of drug",
        "terseLabel": "Sublicense fee paid in stock"
       }
      }
     },
     "localname": "SublicenseFeePaidForLicenseOfDrug",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_UpfrontLicenseFeeToBeReceived": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The amount of upfront license fees expected to be received under the collaboration agreement.",
        "label": "Upfront license fee to be received",
        "terseLabel": "Upfront license fee to be received"
       }
      }
     },
     "localname": "UpfrontLicenseFeeToBeReceived",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_UpfrontPaymentReceivedIncludingPurchaseOfStock": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.",
        "label": "Upfront payment received, including purchase of stock",
        "verboseLabel": "Upfront payment received"
       }
      }
     },
     "localname": "UpfrontPaymentReceivedIncludingPurchaseOfStock",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_WeightedAverageNumberOfSharesOwnedInSubsidiary": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.",
        "label": "Weighted average number of shares owned in subsidiary",
        "terseLabel": "Weighted average shares owned in Akcea (in shares)"
       }
      }
     },
     "localname": "WeightedAverageNumberOfSharesOwnedInSubsidiary",
     "nsuri": "http://isispharm.com/20190930",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "srt_ConsolidatedEntitiesAxis": {
     "auth_ref": [
      "r362"
     ],
     "lang": {
      "en-US": {
       "role": {
        "label": "Consolidated Entities [Axis]"
       }
      }
     },
     "localname": "ConsolidatedEntitiesAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_ConsolidatedEntitiesDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Consolidated Entities [Domain]"
       }
      }
     },
     "localname": "ConsolidatedEntitiesDomain",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ConsolidationItemsAxis": {
     "auth_ref": [
      "r122",
      "r128"
     ],
     "lang": {
      "en-US": {
       "role": {
        "label": "Consolidation Items [Axis]"
       }
      }
     },
     "localname": "ConsolidationItemsAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_ConsolidationItemsDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Consolidation Items [Domain]"
       }
      }
     },
     "localname": "ConsolidationItemsDomain",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_MajorCustomersAxis": {
     "auth_ref": [
      "r131",
      "r189",
      "r193",
      "r345"
     ],
     "lang": {
      "en-US": {
       "role": {
        "label": "Customer [Axis]"
       }
      }
     },
     "localname": "MajorCustomersAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_MinimumMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Minimum [Member]"
       }
      }
     },
     "localname": "MinimumMember",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_NameOfMajorCustomerDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Customer [Domain]"
       }
      }
     },
     "localname": "NameOfMajorCustomerDomain",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_OwnershipAxis": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Ownership [Axis]"
       }
      }
     },
     "localname": "OwnershipAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_OwnershipDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Ownership [Domain]"
       }
      }
     },
     "localname": "OwnershipDomain",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ProductOrServiceAxis": {
     "auth_ref": [
      "r130",
      "r189",
      "r192",
      "r343",
      "r344"
     ],
     "lang": {
      "en-US": {
       "role": {
        "label": "Products and Services [Axis]"
       }
      }
     },
     "localname": "ProductOrServiceAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_ProductsAndServicesDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Products and Services [Domain]"
       }
      }
     },
     "localname": "ProductsAndServicesDomain",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_RangeAxis": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Range [Axis]"
       }
      }
     },
     "localname": "RangeAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_RangeMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Range [Domain]"
       }
      }
     },
     "localname": "RangeMember",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ScenarioForecastMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Forecast [Member]"
       }
      }
     },
     "localname": "ScenarioForecastMember",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ScenarioUnspecifiedDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Scenario [Domain]"
       }
      }
     },
     "localname": "ScenarioUnspecifiedDomain",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_StatementScenarioAxis": {
     "auth_ref": [
      "r181",
      "r305"
     ],
     "lang": {
      "en-US": {
       "role": {
        "label": "Scenario [Axis]"
       }
      }
     },
     "localname": "StatementScenarioAxis",
     "nsuri": "http://fasb.org/srt/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AccountingPoliciesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Significant Accounting Policies [Abstract]"
       }
      }
     },
     "localname": "AccountingPoliciesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_AccountingStandardsUpdate201602Member": {
     "auth_ref": [
      "r286"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Accounting Standards Update 2016-02 Leases (Topic 842).",
        "label": "Accounting Standards Update 2016-02 [Member]",
        "terseLabel": "Topic 842 [Member]"
       }
      }
     },
     "localname": "AccountingStandardsUpdate201602Member",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AccountsPayableCurrent": {
     "auth_ref": [
      "r23"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments": {
     "auth_ref": [
      "r77"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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",
        "negatedLabel": "Amortization of premium (discount) on investments, net"
       }
      }
     },
     "localname": "AccretionAmortizationOfDiscountsAndPremiumsInvestments",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccruedIncomeTaxesCurrent": {
     "auth_ref": [
      "r10",
      "r325",
      "r335"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccruedLiabilitiesCurrent": {
     "auth_ref": [
      "r26"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax": {
     "auth_ref": [
      "r40",
      "r41",
      "r42"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccumulatedOtherComprehensiveIncomeMember": {
     "auth_ref": [
      "r39",
      "r42",
      "r43",
      "r254"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AdditionalPaidInCapitalCommonStock": {
     "auth_ref": [
      "r15"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AdditionalPaidInCapitalMember": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AdjustmentsForNewAccountingPronouncementsAxis": {
     "auth_ref": [
      "r92"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by new accounting pronouncement.",
        "label": "Adjustments for New Accounting Pronouncements [Axis]"
       }
      }
     },
     "localname": "AdjustmentsForNewAccountingPronouncementsAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "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 share-based awards and exercise of employee stock options"
       }
      }
     },
     "localname": "AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue": {
     "auth_ref": [
      "r200",
      "r202",
      "r221",
      "r222"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Adjustments to Reconcile Net Income (Loss) to Cash Provided by (Used in) Operating Activities [Abstract]",
        "terseLabel": "Adjustments to reconcile net loss to net cash provided by operating activities:"
       }
      }
     },
     "localname": "AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AllocatedShareBasedCompensationExpense": {
     "auth_ref": [
      "r202",
      "r215",
      "r220"
     ],
     "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": "Stock-based compensation expense"
       }
      }
     },
     "localname": "AllocatedShareBasedCompensationExpense",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AmortizationOfDebtDiscountPremium": {
     "auth_ref": [
      "r59",
      "r76",
      "r283"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 6.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of noncash expense included in interest expense to amortize debt discount and premium associated with the related debt instruments. Excludes amortization of financing costs. Alternate captions include noncash interest expense.",
        "label": "Amortization of convertible senior notes discount"
       }
      }
     },
     "localname": "AmortizationOfDebtDiscountPremium",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AmortizationOfFinancingCosts": {
     "auth_ref": [
      "r53",
      "r76",
      "r284"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AmortizationOfIntangibleAssets": {
     "auth_ref": [
      "r76",
      "r169",
      "r172"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AssetImpairmentCharges": {
     "auth_ref": [
      "r76",
      "r173"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 12.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of write-down of assets recognized in the income statement. Includes, but is not limited to, losses from tangible assets, intangible assets and goodwill.",
        "label": "Asset Impairment Charges",
        "terseLabel": "Non-cash losses related to patents, licensing and property, plant and equipment"
       }
      }
     },
     "localname": "AssetImpairmentCharges",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_Assets": {
     "auth_ref": [
      "r125",
      "r323",
      "r334"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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": "Total assets as of current period",
        "totalLabel": "Total assets"
       }
      }
     },
     "localname": "Assets",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AssetsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Assets [Abstract]",
        "terseLabel": "ASSETS"
       }
      }
     },
     "localname": "AssetsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AssetsCurrent": {
     "auth_ref": [
      "r4",
      "r5",
      "r36"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AssetsFairValueDisclosure": {
     "auth_ref": [
      "r265"
     ],
     "calculation": {
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax": {
     "auth_ref": [
      "r144"
     ],
     "calculation": {
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax": {
     "auth_ref": [
      "r145"
     ],
     "calculation": {
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis": {
     "auth_ref": [
      "r142",
      "r157"
     ],
     "calculation": {
      "http://isispharm.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": "Cost"
       }
      }
     },
     "localname": "AvailableForSaleDebtSecuritiesAmortizedCostBasis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecurities": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/FairValueMeasurementsDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_AssetsFairValueDisclosure",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of investment in debt and equity securities categorized neither as held-to-maturity nor trading.",
        "label": "Available-for-sale Securities",
        "verboseLabel": "Available-for-sale securities"
       }
      }
     },
     "localname": "AvailableForSaleSecurities",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for twelve months or longer.",
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, 12 Months or Longer, Accumulated Loss",
        "negatedLabel": "Unrealized losses, more than 12 months of temporary impairment"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss": {
     "auth_ref": [
      "r149"
     ],
     "calculation": {
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale in a continuous loss position.",
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, Accumulated Loss",
        "negatedTotalLabel": "Unrealized losses, total temporary impairment"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "This item represents the aggregate fair value of investments in debt and equity securities in an unrealized loss position which are categorized neither as held-to-maturity nor trading securities.",
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, Fair Value",
        "totalLabel": "Estimated fair value, total temporary impairment"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 2.0,
       "parentTag": "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of accumulated unrealized loss on investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for less than twelve months.",
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, Less than 12 Months, Accumulated Loss",
        "negatedLabel": "Unrealized losses, less than 12 months of temporary impairment"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for less than twelve months.",
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, Less than Twelve Months, Fair Value",
        "terseLabel": "Estimated fair value, less than 12 months of temporary impairment"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for twelve months or longer.",
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, Twelve Months or Longer, Fair Value",
        "terseLabel": "Estimated fair value, more than 12 months of temporary impairment"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesDebtSecurities": {
     "auth_ref": [
      "r139",
      "r143",
      "r157"
     ],
     "calculation": {
      "http://isispharm.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"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtSecurities",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent": {
     "auth_ref": [
      "r141",
      "r157"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Summary of Investments [Abstract]"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1": {
     "auth_ref": [
      "r147"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Number of investment positions in available-for-sale investments in a continuous unrealized loss position for which an other-than-temporary impairment (OTTI) has not been recognized in the income statement.",
        "label": "Available-for-sale, Securities in Unrealized Loss Positions, Qualitative Disclosure, Number of Positions",
        "terseLabel": "Number of investments"
       }
      }
     },
     "localname": "AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "us-gaap_AwardTypeAxis": {
     "auth_ref": [
      "r203",
      "r217"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_BalanceSheetLocationDomain": {
     "auth_ref": [
      "r263",
      "r264"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_CapitalExpendituresIncurredButNotYetPaid": {
     "auth_ref": [
      "r80",
      "r81",
      "r82"
     ],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Future cash outflow to pay for purchases of fixed assets that have occurred.",
        "label": "Capital Expenditures Incurred but Not yet Paid",
        "terseLabel": "Purchases of property, plant and equipment included in long-term obligations"
       }
      }
     },
     "localname": "CapitalExpendituresIncurredButNotYetPaid",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashAndCashEquivalentsAtCarryingValue": {
     "auth_ref": [
      "r2",
      "r20",
      "r78"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashAndCashEquivalentsFairValueDisclosure": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents": {
     "auth_ref": [
      "r71",
      "r78",
      "r83"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect": {
     "auth_ref": [
      "r71",
      "r277"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of increase (decrease) in cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; excluding 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), Excluding Exchange Rate Effect",
        "totalLabel": "Net increase in cash and cash equivalents"
       }
      }
     },
     "localname": "CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ClassOfStockDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Share of stock differentiated by the voting rights the holder receives. Examples include, but are not limited to, common stock, redeemable preferred stock, nonredeemable preferred stock, and convertible stock.",
        "label": "Class of Stock [Domain]"
       }
      }
     },
     "localname": "ClassOfStockDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CollaborativeArrangementDisclosureTextBlock": {
     "auth_ref": [
      "r240",
      "r241",
      "r243"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CommonStockCapitalSharesReservedForFutureIssuance": {
     "auth_ref": [
      "r30"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Aggregate number of common shares reserved for future issuance.",
        "label": "Common Stock, Capital Shares Reserved for Future Issuance",
        "terseLabel": "Common shares reserved for future issuance (in shares)"
       }
      }
     },
     "localname": "CommonStockCapitalSharesReservedForFutureIssuance",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockMember": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CommonStockParOrStatedValuePerShare": {
     "auth_ref": [
      "r14"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_CommonStockSharesAuthorized": {
     "auth_ref": [
      "r14"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockSharesIssued": {
     "auth_ref": [
      "r14"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockSharesOutstanding": {
     "auth_ref": [
      "r14",
      "r183"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockValue": {
     "auth_ref": [
      "r14"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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, 140,636,397 and 137,928,828 shares issued and outstanding at September 30, 2019 (unaudited) and December 31, 2018, respectively"
       }
      }
     },
     "localname": "CommonStockValue",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ComprehensiveIncomeNetOfTax": {
     "auth_ref": [
      "r45",
      "r47",
      "r48"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited": {
       "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 income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders"
       }
      }
     },
     "localname": "ComprehensiveIncomeNetOfTax",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest": {
     "auth_ref": [
      "r45",
      "r47",
      "r247",
      "r248",
      "r258"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited": {
       "order": 1.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTax",
       "weight": -1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income (loss) and other comprehensive income (loss), attributable to noncontrolling interests. Excludes changes in equity resulting from investments by owners and distributions to owners.",
        "label": "Comprehensive Income (Loss), Net of Tax, Attributable to Noncontrolling Interest",
        "terseLabel": "Comprehensive loss attributable to noncontrolling interests"
       }
      }
     },
     "localname": "ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest": {
     "auth_ref": [
      "r45",
      "r47",
      "r246",
      "r258"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited": {
       "order": 0.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTax",
       "weight": 1.0
      }
     },
     "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. Excludes changes in equity resulting from investments by owners and distributions to owners.",
        "label": "Comprehensive Income (Loss), Net of Tax, Including Portion Attributable to Noncontrolling Interest",
        "totalLabel": "Comprehensive income (loss)"
       }
      }
     },
     "localname": "ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ConcentrationRiskBenchmarkDomain": {
     "auth_ref": [
      "r115",
      "r116",
      "r274",
      "r275"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ConcentrationRiskByBenchmarkAxis": {
     "auth_ref": [
      "r115",
      "r116",
      "r274",
      "r275",
      "r347"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by benchmark of concentration risk.",
        "label": "Concentration Risk Benchmark [Axis]"
       }
      }
     },
     "localname": "ConcentrationRiskByBenchmarkAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ConcentrationRiskByTypeAxis": {
     "auth_ref": [
      "r115",
      "r116",
      "r274",
      "r275",
      "r347"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ConcentrationRiskPercentage1": {
     "auth_ref": [
      "r115",
      "r116",
      "r274",
      "r275"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ConcentrationRiskTypeDomain": {
     "auth_ref": [
      "r115",
      "r116",
      "r274",
      "r275"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ConsolidationPolicyTextBlock": {
     "auth_ref": [
      "r84",
      "r249",
      "r259",
      "r260"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy": {
     "auth_ref": [
      "r84",
      "r87",
      "r249",
      "r259",
      "r260",
      "r261"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Disclosure of accounting policy for subsidiaries or other investments that are consolidated, including the accounting treatment for intercompany accounts or transactions and any noncontrolling interest.",
        "label": "Consolidation, Subsidiaries or Other Investments, Consolidated Entities, Policy [Policy Text Block]",
        "terseLabel": "Noncontrolling Interest in Akcea Therapeutics, Inc."
       }
      }
     },
     "localname": "ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ContractWithCustomerAssetNetCurrent": {
     "auth_ref": [
      "r185",
      "r187",
      "r190"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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, Net, Current",
        "terseLabel": "Contracts receivable"
       }
      }
     },
     "localname": "ContractWithCustomerAssetNetCurrent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiability": {
     "auth_ref": [
      "r185",
      "r186",
      "r190"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityCurrent": {
     "auth_ref": [
      "r185",
      "r186",
      "r190"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 6.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityNoncurrent": {
     "auth_ref": [
      "r185",
      "r186",
      "r190"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityRevenueRecognized": {
     "auth_ref": [
      "r191"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ConvertibleDebtNoncurrent": {
     "auth_ref": [
      "r29"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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": "1 percent convertible senior notes"
       }
      }
     },
     "localname": "ConvertibleDebtNoncurrent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ConvertiblePreferredStockMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Preferred stock that may be exchanged into common shares or other types of securities at the owner's option.",
        "label": "Convertible Preferred Stock [Member]",
        "terseLabel": "Preferred Stock [Member]"
       }
      }
     },
     "localname": "ConvertiblePreferredStockMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CorporateDebtSecuritiesMember": {
     "auth_ref": [
      "r196",
      "r199",
      "r346"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CostOfGoodsAndServicesSold": {
     "auth_ref": [
      "r56"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "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 products sold"
       }
      }
     },
     "localname": "CostOfGoodsAndServicesSold",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CostOfGoodsAndServicesSoldAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Cost of Goods and Services Sold [Abstract]",
        "terseLabel": "Cost of Products Sold [Abstract]"
       }
      }
     },
     "localname": "CostOfGoodsAndServicesSoldAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "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 Products Sold [Member]"
       }
      }
     },
     "localname": "CostOfSalesMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CostOfSalesPolicyTextBlock": {
     "auth_ref": [
      "r195"
     ],
     "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 Products Sold"
       }
      }
     },
     "localname": "CostOfSalesPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_CostsAndExpenses": {
     "auth_ref": [
      "r54"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "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",
        "verboseLabel": "Total operating expenses"
       }
      }
     },
     "localname": "CostsAndExpenses",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CustomerConcentrationRiskMember": {
     "auth_ref": [
      "r114"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_DebtInstrumentAxis": {
     "auth_ref": [
      "r9",
      "r10",
      "r11",
      "r324",
      "r326",
      "r333"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DebtInstrumentInterestRateStatedPercentage": {
     "auth_ref": [
      "r28"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Contractual interest rate for funds borrowed, under the debt agreement.",
        "label": "Debt Instrument, Interest Rate, Stated Percentage",
        "terseLabel": "Interest rate on convertible senior notes"
       }
      }
     },
     "localname": "DebtInstrumentInterestRateStatedPercentage",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_DebtInstrumentNameDomain": {
     "auth_ref": [
      "r29"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_DebtPolicyTextBlock": {
     "auth_ref": [
      "r84",
      "r182"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_DebtSecuritiesMember": {
     "auth_ref": [
      "r150"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_DeferredIncomeTaxExpenseBenefit": {
     "auth_ref": [
      "r76",
      "r88",
      "r234",
      "r236"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 14.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of deferred income tax expense (benefit) pertaining to income (loss) from continuing operations.",
        "label": "Deferred Income Tax Expense (Benefit)",
        "terseLabel": "Provision for deferred income taxes"
       }
      }
     },
     "localname": "DeferredIncomeTaxExpenseBenefit",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent": {
     "auth_ref": [
      "r226",
      "r227",
      "r232"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 5.0,
       "parentTag": "us-gaap_Assets",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount, after allocation of valuation allowances and deferred tax liability, of deferred tax asset attributable to deductible differences and carryforwards, with jurisdictional netting and classified as noncurrent.",
        "label": "Deferred Tax Assets, Net, Noncurrent",
        "terseLabel": "Long-term deferred tax assets"
       }
      }
     },
     "localname": "DeferredTaxAssetsLiabilitiesNetNoncurrent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_Depreciation": {
     "auth_ref": [
      "r76",
      "r174"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DisaggregationOfRevenueTable": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Share-based Payment Arrangement [Abstract]",
        "terseLabel": "Stock-based Compensation Expense [Abstract]"
       }
      }
     },
     "localname": "DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EarningsPerShareBasic": {
     "auth_ref": [
      "r52",
      "r93",
      "r98",
      "r101",
      "r102",
      "r103",
      "r107",
      "r331",
      "r342"
     ],
     "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 income (loss) per share (in dollars per share)"
       }
      }
     },
     "localname": "EarningsPerShareBasic",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_EarningsPerShareBasicAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Basic Net Income (Loss) per Share [Abstract]"
       }
      }
     },
     "localname": "EarningsPerShareBasicAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EarningsPerShareDiluted": {
     "auth_ref": [
      "r52",
      "r93",
      "r98",
      "r101",
      "r102",
      "r103",
      "r107",
      "r331",
      "r342"
     ],
     "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 income (loss) per share (in dollars per share)",
        "terseLabel": "Diluted net income per share (in dollars per share)"
       }
      }
     },
     "localname": "EarningsPerShareDiluted",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_EarningsPerSharePolicyTextBlock": {
     "auth_ref": [
      "r84",
      "r104",
      "r105",
      "r106"
     ],
     "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 Income (Loss) per Share"
       }
      }
     },
     "localname": "EarningsPerSharePolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_EffectiveIncomeTaxRateContinuingOperations": {
     "auth_ref": [
      "r90",
      "r228",
      "r229"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Percentage of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.",
        "label": "Effective Income Tax Rate Reconciliation, Percent",
        "terseLabel": "Effective tax rate"
       }
      }
     },
     "localname": "EffectiveIncomeTaxRateContinuingOperations",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/IncomeTaxesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Effective Income Tax Rate Reconciliation, Percent [Abstract]",
        "verboseLabel": "Income Taxes [Abstract]"
       }
      }
     },
     "localname": "EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/IncomeTaxesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate": {
     "auth_ref": [
      "r228",
      "r229",
      "r235"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Percentage of domestic federal statutory tax rate applicable to pretax income (loss).",
        "label": "Effective Income Tax Rate Reconciliation, at Federal Statutory Income Tax Rate, Percent",
        "terseLabel": "Federal statutory rate"
       }
      }
     },
     "localname": "EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/IncomeTaxesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_EmployeeRelatedLiabilitiesCurrent": {
     "auth_ref": [
      "r26"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1": {
     "auth_ref": [
      "r216"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions": {
     "auth_ref": [
      "r216"
     ],
     "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 RSUs"
       }
      }
     },
     "localname": "EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions": {
     "auth_ref": [
      "r216"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_EmployeeStockOptionMember": {
     "auth_ref": [
      "r213"
     ],
     "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": "Employee Stock Options [Member]",
        "verboseLabel": "Stock Options [Member]"
       }
      }
     },
     "localname": "EmployeeStockOptionMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_EquityComponentDomain": {
     "auth_ref": [
      "r183"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_EquitySecuritiesFvNi": {
     "auth_ref": [
      "r273"
     ],
     "calculation": {
      "http://isispharm.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).",
        "label": "Equity Securities, FV-NI",
        "terseLabel": "Investment in ProQR Therapeutics N.V.",
        "verboseLabel": "Estimated fair value"
       }
      }
     },
     "localname": "EquitySecuritiesFvNi",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.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": "Cost"
       }
      }
     },
     "localname": "EquitySecuritiesFvNiCost",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EquitySecuritiesFvNiUnrealizedGain": {
     "auth_ref": [
      "r151"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EquitySecuritiesFvNiUnrealizedLoss": {
     "auth_ref": [
      "r151"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable": {
     "auth_ref": [
      "r265",
      "r266",
      "r267",
      "r271"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock": {
     "auth_ref": [
      "r265",
      "r266"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_FairValueByFairValueHierarchyLevelAxis": {
     "auth_ref": [
      "r196",
      "r197",
      "r199",
      "r266",
      "r306"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueByMeasurementFrequencyAxis": {
     "auth_ref": [
      "r265",
      "r266",
      "r268",
      "r269",
      "r272"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by measurement frequency.",
        "label": "Measurement Frequency [Axis]"
       }
      }
     },
     "localname": "FairValueByMeasurementFrequencyAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueDisclosuresTextBlock": {
     "auth_ref": [
      "r270"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurements"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_FairValueInputsLevel1Member": {
     "auth_ref": [
      "r196",
      "r197",
      "r199",
      "r266",
      "r307"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueInputsLevel2Member": {
     "auth_ref": [
      "r196",
      "r197",
      "r199",
      "r266",
      "r308"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueInputsLevel3Member": {
     "auth_ref": [
      "r196",
      "r197",
      "r199",
      "r266",
      "r309"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueMeasurementsFairValueHierarchyDomain": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueMeasurementsRecurringMember": {
     "auth_ref": [
      "r270",
      "r272"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FinancialInstrumentAxis": {
     "auth_ref": [
      "r152",
      "r153",
      "r154",
      "r155",
      "r156",
      "r159",
      "r160",
      "r161",
      "r162"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by type of financial instrument.",
        "label": "Financial Instrument [Axis]"
       }
      }
     },
     "localname": "FinancialInstrumentAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FiniteLivedIntangibleAssetsNet": {
     "auth_ref": [
      "r171"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments": {
     "auth_ref": [
      "r89"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 0.0,
       "parentTag": "us-gaap_ProfitLoss",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of income (loss) from continuing operations before deduction of income tax expense (benefit) and income (loss) attributable to noncontrolling interest, and addition of income (loss) from equity method investments.",
        "label": "Income (Loss) from Continuing Operations before Equity Method Investments, Income Taxes, Noncontrolling Interest",
        "totalLabel": "Income (loss) before income tax (expense) benefit"
       }
      }
     },
     "localname": "IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncomeStatementAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) [Abstract]"
       }
      }
     },
     "localname": "IncomeStatementAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncomeStatementLocationAxis": {
     "auth_ref": [
      "r177"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncomeStatementLocationDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Location in the income statement.",
        "label": "Income Statement Location [Domain]"
       }
      }
     },
     "localname": "IncomeStatementLocationDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncomeTaxDisclosureTextBlock": {
     "auth_ref": [
      "r239"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/IncomeTaxes"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_IncomeTaxExpenseBenefit": {
     "auth_ref": [
      "r88",
      "r124",
      "r237"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 1.0,
       "parentTag": "us-gaap_ProfitLoss",
       "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) benefit",
        "terseLabel": "Income tax expense (benefit)"
       }
      }
     },
     "localname": "IncomeTaxExpenseBenefit",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/IncomeTaxesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncomeTaxPolicyTextBlock": {
     "auth_ref": [
      "r49",
      "r84",
      "r224",
      "r225",
      "r230",
      "r231",
      "r233",
      "r238",
      "r361"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_IncomeTaxesPaid": {
     "auth_ref": [
      "r73",
      "r79"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInAccountsPayable": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 18.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInContractWithCustomerAsset": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 15.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInContractWithCustomerLiability": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 21.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInInventories": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 16.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 19.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInOtherOperatingAssets": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 17.0,
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements": {
     "auth_ref": [
      "r99",
      "r105"
     ],
     "calculation": {
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding",
       "weight": 1.0
      }
     },
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of share based payment arrangements using the treasury stock method.",
        "label": "Shares issuable related to stock-based compensation (in shares)"
       }
      }
     },
     "localname": "IncrementalCommonSharesAttributableToShareBasedPaymentArrangements",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_IntangibleAssetsFiniteLivedPolicy": {
     "auth_ref": [
      "r84",
      "r170"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_InterestExpense": {
     "auth_ref": [
      "r50",
      "r123",
      "r282",
      "r284",
      "r332"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 4.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments",
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InterestPaidNet": {
     "auth_ref": [
      "r69",
      "r72",
      "r79"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IntersegmentEliminationMember": {
     "auth_ref": [
      "r127"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Eliminating entries used in operating segment consolidation.",
        "label": "Elimination of Intercompany Activity [Member]"
       }
      }
     },
     "localname": "IntersegmentEliminationMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_InventoryNet": {
     "auth_ref": [
      "r3",
      "r33",
      "r164"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 3.0,
       "parentTag": "us-gaap_AssetsCurrent",
       "weight": 1.0
      }
     },
     "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"
       }
      }
     },
     "localname": "InventoryNet",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InventoryPolicyTextBlock": {
     "auth_ref": [
      "r6",
      "r34",
      "r84",
      "r108",
      "r165",
      "r167"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Inventory, Raw Materials and Supplies, Net of Reserves [Abstract]",
        "terseLabel": "Inventory Valuation [Abstract]"
       }
      }
     },
     "localname": "InventoryRawMaterialsAndSuppliesNetOfReservesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InventoryWriteDown": {
     "auth_ref": [
      "r166"
     ],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of loss from reductions in inventory due to subsequent measurement adjustments, including, but not limited to, physical deterioration, obsolescence, or changes in price levels.",
        "label": "Inventory Write-down",
        "terseLabel": "Inventory write-off"
       }
      }
     },
     "localname": "InventoryWriteDown",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentHoldingsTable": {
     "auth_ref": [
      "r349",
      "r354",
      "r358",
      "r359"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentIncomeNet": {
     "auth_ref": [
      "r58",
      "r59",
      "r60"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 3.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments",
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InvestmentSecondaryCategorizationAxis": {
     "auth_ref": [
      "r352",
      "r353",
      "r355",
      "r356"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentTypeAxis": {
     "auth_ref": [
      "r348",
      "r351",
      "r357",
      "r360"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by type of investments.",
        "label": "Investment Type [Axis]"
       }
      }
     },
     "localname": "InvestmentTypeAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentTypeCategorizationMember": {
     "auth_ref": [
      "r348",
      "r351",
      "r357",
      "r360"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Asset obtained to generate income or appreciate in value.",
        "label": "Investments [Domain]"
       }
      }
     },
     "localname": "InvestmentTypeCategorizationMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_InvestmentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Investments [Abstract]"
       }
      }
     },
     "localname": "InvestmentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentsBySecondaryCategorizationDomain": {
     "auth_ref": [
      "r350",
      "r355"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_LeasesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Operating Leases [Abstract]"
       }
      }
     },
     "localname": "LeasesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_LesseeDisclosureAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Lessee Disclosure [Abstract]",
        "terseLabel": "Operating Leases [Abstract]"
       }
      }
     },
     "localname": "LesseeDisclosureAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.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": "Operating Leased Assets [Line Items]"
       }
      }
     },
     "localname": "LesseeLeaseDescriptionLineItems",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LesseeLeaseDescriptionTable": {
     "auth_ref": [
      "r293"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Disclosure of information about lessee's leases.",
        "label": "Schedule of Operating Leased Assets [Table]"
       }
      }
     },
     "localname": "LesseeLeaseDescriptionTable",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LesseeLeasesPolicyTextBlock": {
     "auth_ref": [
      "r291"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      },
      "http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due",
        "totalLabel": "Total minimum lease payments"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDue",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": 5.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease, due after fifth fiscal year following latest fiscal year.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due after Year Five",
        "terseLabel": "Thereafter"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease, due in next fiscal year following latest fiscal year.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due Next Twelve Months",
        "terseLabel": "Remainder of 2019"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": 4.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease, due in fifth fiscal year following latest fiscal year.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due Year Five",
        "terseLabel": "2023"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDueYearFive",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": 3.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease, due in fourth fiscal year following latest fiscal year.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due Year Four",
        "terseLabel": "2022"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDueYearFour",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": 2.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease, due in third fiscal year following latest fiscal year.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due Year Three",
        "terseLabel": "2021"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDueYearThree",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OperatingLeasesDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments for operating lease, due in second fiscal year following latest fiscal year.",
        "label": "Lessee, Operating Lease, Liability, Payments, Due Year Two",
        "terseLabel": "2020"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDueYearTwo",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount": {
     "auth_ref": [
      "r298"
     ],
     "calculation": {
      "http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2": {
       "order": 0.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payments in excess of discounted obligation for lease payments for operating lease.",
        "label": "Lessee, Operating Lease, Liability, Undiscounted Excess Amount",
        "negatedLabel": "Imputed interest"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityUndiscountedExcessAmount",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LesseeOperatingLeaseRenewalTerm": {
     "auth_ref": [
      "r292"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.",
        "label": "Lessee, Operating Lease, Renewal Term",
        "terseLabel": "Term of lease extension"
       }
      }
     },
     "localname": "LesseeOperatingLeaseRenewalTerm",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_LesseeOperatingLeaseTermOfContract": {
     "auth_ref": [
      "r292"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.",
        "label": "Lessee, Operating Lease, Term of Contract",
        "terseLabel": "Term of lease"
       }
      }
     },
     "localname": "LesseeOperatingLeaseTermOfContract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_LesseeOperatingLeasesTextBlock": {
     "auth_ref": [
      "r300"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The entire disclosure for operating leases of lessee. Includes, but is not limited to, description of operating lease and maturity analysis of operating lease liability.",
        "label": "Lessee, Operating Leases [Text Block]",
        "terseLabel": "Operating Leases"
       }
      }
     },
     "localname": "LesseeOperatingLeasesTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeases"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_Liabilities": {
     "auth_ref": [
      "r25"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LiabilitiesAndStockholdersEquity": {
     "auth_ref": [
      "r19",
      "r328",
      "r339"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LiabilitiesCurrent": {
     "auth_ref": [
      "r27"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LicenseMember": {
     "auth_ref": [
      "r192"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Right to use intangible asset. Intangible asset includes, but is not limited to, patent, copyright, technology, manufacturing process, software or trademark.",
        "label": "License [Member]",
        "terseLabel": "License Fees [Member]"
       }
      }
     },
     "localname": "LicenseMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent": {
     "auth_ref": [
      "r26"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 5.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of long-term debt and lease obligation, classified as current.",
        "label": "Long-term Debt and Lease Obligation, Current",
        "terseLabel": "Current portion of long-term obligations"
       }
      }
     },
     "localname": "LongTermDebtAndCapitalLeaseObligationsCurrent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LongTermLoansFromBank": {
     "auth_ref": [
      "r11",
      "r326",
      "r336"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_MinorityInterest": {
     "auth_ref": [
      "r32",
      "r327",
      "r338"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 1.0,
       "parentTag": "us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest",
       "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 is directly or indirectly attributable to that ownership interest in subsidiary equity which is not attributable to the parent (that is, noncontrolling interest, previously referred to as minority interest).",
        "label": "Noncontrolling interest in Akcea Therapeutics, Inc."
       }
      }
     },
     "localname": "MinorityInterest",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_MinorityInterestLineItems": {
     "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": "Noncontrolling Interest [Line Items]"
       }
      }
     },
     "localname": "MinorityInterestLineItems",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_MinorityInterestOwnershipPercentageByParent": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The parent entity's interest in net assets of the subsidiary, expressed as a percentage.",
        "label": "Noncontrolling Interest, Ownership Percentage by Parent",
        "terseLabel": "Percentage ownership"
       }
      }
     },
     "localname": "MinorityInterestOwnershipPercentageByParent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_MinorityInterestPeriodIncreaseDecrease": {
     "auth_ref": [
      "r245"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Net Increase or Decrease in balance of noncontrolling interest in the subsidiary during the reporting period.",
        "label": "Noncontrolling Interest, Period Increase (Decrease)",
        "terseLabel": "Noncontrolling interest in Akcea Therapetuics, Inc."
       }
      }
     },
     "localname": "MinorityInterestPeriodIncreaseDecrease",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_MinorityInterestTable": {
     "auth_ref": [
      "r32",
      "r55",
      "r245",
      "r255"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Schedule of noncontrolling interest disclosure which includes the name of the subsidiary, the ownership percentage held by the parent, the ownership percentage held by the noncontrolling owners, the amount of the noncontrolling interest, the location of this amount on the balance sheet (when not reported separately), an explanation of the increase or decrease in the amount of the noncontrolling interest, the noncontrolling interest share of the net Income or Loss of the subsidiary, the location of this amount on the income statement (when not reported separately), the nature of the noncontrolling interest such as background information and terms, the amount of the noncontrolling interest represented by preferred stock, a description of the preferred stock, and the dividend requirements of the preferred stock.",
        "label": "Noncontrolling Interest [Table]"
       }
      }
     },
     "localname": "MinorityInterestTable",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetCashProvidedByUsedInFinancingActivities": {
     "auth_ref": [
      "r71"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 4.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect",
       "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 provided by financing activities"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInFinancingActivities",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetCashProvidedByUsedInInvestingActivities": {
     "auth_ref": [
      "r71"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 3.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect",
       "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 investing activities"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInInvestingActivities",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetCashProvidedByUsedInOperatingActivities": {
     "auth_ref": [
      "r71",
      "r74",
      "r77"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 2.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect",
       "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 provided by operating activities"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInOperatingActivities",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetIncomeLoss": {
     "auth_ref": [
      "r44",
      "r46",
      "r51",
      "r77",
      "r105",
      "r330",
      "r341"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "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 income (loss)",
        "totalLabel": "Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders",
        "verboseLabel": "Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders"
       }
      }
     },
     "localname": "NetIncomeLoss",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetIncomeLossAttributableToNoncontrollingInterest": {
     "auth_ref": [
      "r44",
      "r46",
      "r251",
      "r257"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 1.0,
       "parentTag": "us-gaap_NetIncomeLoss",
       "weight": -1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of Net Income (Loss) attributable to noncontrolling interest.",
        "label": "Net Income (Loss) Attributable to Noncontrolling Interest",
        "negatedTerseLabel": "Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc."
       }
      }
     },
     "localname": "NetIncomeLossAttributableToNoncontrollingInterest",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic": {
     "auth_ref": [
      "r93",
      "r96"
     ],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.",
        "label": "Net income (loss) available to Ionis common shareholders"
       }
      }
     },
     "localname": "NetIncomeLossAvailableToCommonStockholdersBasic",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted": {
     "auth_ref": [
      "r96",
      "r97"
     ],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities, and addition from assumption of issuance of common shares for dilutive potential common shares; of income (loss) available to common shareholders.",
        "label": "Net Income (Loss) Available to Common Stockholders, Diluted",
        "verboseLabel": "Income available to Ionis common shareholders"
       }
      }
     },
     "localname": "NetIncomeLossAvailableToCommonStockholdersDiluted",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems": {
     "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": "New Accounting Pronouncements or Change in Accounting Principle [Line Items]"
       }
      }
     },
     "localname": "NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable": {
     "auth_ref": [
      "r92",
      "r94"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Summarization of the changes in an accounting principle or a new accounting pronouncement, including the line items affected by the change and the financial effects of the change on those particular line items.",
        "label": "New Accounting Pronouncements or Change in Accounting Principle [Table]"
       }
      }
     },
     "localname": "NewAccountingPronouncementsOrChangeInAccountingPrincipleTable",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_NoncontrollingInterestAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Noncontrolling Interest [Abstract]",
        "verboseLabel": "Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]"
       }
      }
     },
     "localname": "NoncontrollingInterestAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NoncontrollingInterestMember": {
     "auth_ref": [
      "r244"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "This element represents that portion of equity (net assets) in a subsidiary not attributable, directly or indirectly, to the parent. A noncontrolling interest is sometimes called a minority interest.",
        "label": "Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]"
       }
      }
     },
     "localname": "NoncontrollingInterestMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "domainItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NotesPayableFairValueDisclosure": {
     "auth_ref": [
      "r24"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NumberOfOperatingSegments": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "us-gaap_NumberOfReportableSegments": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Number of segments reported by the entity. A reportable segment is a component of an entity for which there is an accounting requirement to report separate financial information on that component in the entity's financial statements.",
        "label": "Number of reportable segments"
       }
      }
     },
     "localname": "NumberOfReportableSegments",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "us-gaap_OperatingIncomeLoss": {
     "auth_ref": [],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 1.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments",
       "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": "Income (loss) from operations",
        "verboseLabel": "Income (loss) from operations"
       }
      }
     },
     "localname": "OperatingIncomeLoss",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeaseExpense": {
     "auth_ref": [
      "r289"
     ],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of operating lease expense. Excludes sublease income.",
        "label": "Rent expense"
       }
      }
     },
     "localname": "OperatingLeaseExpense",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Lessee, Operating Lease, Liability, Payment, Due [Abstract]",
        "terseLabel": "Annual Future Minimum Payments Under Operating Leases [Abstract]"
       }
      }
     },
     "localname": "OperatingLeaseLiabilitiesPaymentsDueAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_OperatingLeaseLiability": {
     "auth_ref": [
      "r288"
     ],
     "calculation": {
      "http://isispharm.com/role/OtherObligationsOperatingLeasesDetailsCalc2": {
       "order": 2.0,
       "parentTag": "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Present value of lessee's discounted obligation for lease payments from operating lease.",
        "label": "Operating Lease, Liability",
        "terseLabel": "Total operating lease liabilities",
        "verboseLabel": "Operating lease liabilities"
       }
      }
     },
     "localname": "OperatingLeaseLiability",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeaseLiabilityCurrent": {
     "auth_ref": [
      "r288"
     ],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.",
        "label": "Operating Lease, Liability, Current",
        "terseLabel": "Current portion of operating lease liabilties"
       }
      }
     },
     "localname": "OperatingLeaseLiabilityCurrent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeasePayments": {
     "auth_ref": [
      "r290",
      "r294"
     ],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of cash outflow from operating lease, excluding payments to bring another asset to condition and location necessary for its intended use.",
        "label": "Operating Lease, Payments",
        "terseLabel": "Operating lease cash payments"
       }
      }
     },
     "localname": "OperatingLeasePayments",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeaseRightOfUseAsset": {
     "auth_ref": [
      "r287"
     ],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of lessee's right to use underlying asset under operating lease.",
        "label": "Operating Lease, Right-of-Use Asset",
        "terseLabel": "Right-of-use operating lease assets"
       }
      }
     },
     "localname": "OperatingLeaseRightOfUseAsset",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent": {
     "auth_ref": [
      "r297",
      "r299"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Weighted average discount rate for operating lease calculated at point in time.",
        "label": "Operating Lease, Weighted Average Discount Rate, Percent",
        "terseLabel": "Weighted average discount rate"
       }
      }
     },
     "localname": "OperatingLeaseWeightedAverageDiscountRatePercent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1": {
     "auth_ref": [
      "r296",
      "r299"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Weighted average remaining lease term for operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.",
        "label": "Operating Lease, Weighted Average Remaining Lease Term",
        "terseLabel": "Weighted average remaining lease term"
       }
      }
     },
     "localname": "OperatingLeaseWeightedAverageRemainingLeaseTerm1",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_OperatingSegmentsMember": {
     "auth_ref": [
      "r122",
      "r128"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Identifies components of an entity that engage in business activities from which they may earn revenue and incur expenses, including transactions with other components of the same entity.",
        "label": "Operating Segments [Member]"
       }
      }
     },
     "localname": "OperatingSegmentsMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Basis of Presentation [Abstract]"
       }
      }
     },
     "localname": "OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock": {
     "auth_ref": [
      "r1",
      "r262"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentation"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_OtherAssetsCurrent": {
     "auth_ref": [
      "r35"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherAssetsNoncurrent": {
     "auth_ref": [
      "r22"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent": {
     "auth_ref": [
      "r246",
      "r247",
      "r253"
     ],
     "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": "Other Comprehensive Income (Loss), Available-for-sale Securities Adjustment, Net of Tax, Portion Attributable to Parent",
        "terseLabel": "Change in unrealized gains (losses), net of tax"
       }
      }
     },
     "localname": "OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax": {
     "auth_ref": [
      "r37",
      "r40",
      "r278",
      "r279",
      "r280",
      "r281"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited": {
       "order": 3.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest",
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax": {
     "auth_ref": [
      "r38",
      "r40"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited": {
       "order": 1.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount after tax, before reclassification adjustments, of unrealized holding gain (loss) on available-for-sale securities.",
        "label": "Unrealized gains (losses) on debt securities, net of tax"
       }
      }
     },
     "localname": "OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherDebtSecuritiesMember": {
     "auth_ref": [
      "r146",
      "r158",
      "r196",
      "r270"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_OtherNonoperatingIncomeExpense": {
     "auth_ref": [
      "r60"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 7.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments",
       "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 (expenses)"
       }
      }
     },
     "localname": "OtherNonoperatingIncomeExpense",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ParentMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Portion of equity, or net assets, in the consolidated entity attributable, directly or indirectly, to the parent. Excludes noncontrolling interests.",
        "label": "Total Ionis Stockholders' Equity [Member]"
       }
      }
     },
     "localname": "ParentMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation": {
     "auth_ref": [
      "r67"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt": {
     "auth_ref": [
      "r62",
      "r64",
      "r140"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsToAcquirePropertyPlantAndEquipment": {
     "auth_ref": [
      "r65"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PlanNameAxis": {
     "auth_ref": [
      "r203",
      "r217"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by plan name for share-based payment arrangement.",
        "label": "Plan Name [Axis]"
       }
      }
     },
     "localname": "PlanNameAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_PlanNameDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Plan name for share-based payment arrangement.",
        "label": "Plan Name [Domain]"
       }
      }
     },
     "localname": "PlanNameDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ProceedsFromIssuanceOfCommonStock": {
     "auth_ref": [
      "r66"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 12.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInFinancingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The cash inflow from the additional capital contribution to the entity.",
        "label": "Proceeds from Issuance of Common Stock",
        "verboseLabel": "Proceeds from the issuance of common stock to Biogen"
       }
      }
     },
     "localname": "ProceedsFromIssuanceOfCommonStock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions": {
     "auth_ref": [
      "r66",
      "r218"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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 awards"
       }
      }
     },
     "localname": "ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Proceeds from Issuance or Sale of Equity [Abstract]",
        "terseLabel": "Basis of Presentation [Abstract]"
       }
      }
     },
     "localname": "ProceedsFromIssuanceOrSaleOfEquityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/BasisOfPresentationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities": {
     "auth_ref": [
      "r62",
      "r63",
      "r140"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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 short-term investments"
       }
      }
     },
     "localname": "ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ProductMember": {
     "auth_ref": [
      "r192"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Article or substance produced by nature, labor or machinery.",
        "label": "Product [Member]",
        "terseLabel": "Product Sales, Net [Member]"
       }
      }
     },
     "localname": "ProductMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ProfitLoss": {
     "auth_ref": [
      "r44",
      "r46",
      "r70",
      "r125",
      "r129",
      "r246",
      "r250",
      "r252",
      "r257",
      "r258"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 0.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      },
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited": {
       "order": 0.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest",
       "weight": 1.0
      },
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "order": 0.0,
       "parentTag": "us-gaap_NetIncomeLoss",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.",
        "label": "Net Income (Loss), Including Portion Attributable to Noncontrolling Interest",
        "terseLabel": "Net income (loss)",
        "totalLabel": "Net income (loss)"
       }
      }
     },
     "localname": "ProfitLoss",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PropertyPlantAndEquipmentByTypeAxis": {
     "auth_ref": [
      "r21",
      "r176"
     ],
     "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": "Property, Plant and Equipment, Type [Axis]"
       }
      }
     },
     "localname": "PropertyPlantAndEquipmentByTypeAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_PropertyPlantAndEquipmentNet": {
     "auth_ref": [
      "r7",
      "r8",
      "r176",
      "r340"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PropertyPlantAndEquipmentTypeDomain": {
     "auth_ref": [
      "r7",
      "r175"
     ],
     "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": "Property, Plant and Equipment, Type [Domain]"
       }
      }
     },
     "localname": "PropertyPlantAndEquipmentTypeDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ReceivablesPolicyTextBlock": {
     "auth_ref": [
      "r84",
      "r133",
      "r135",
      "r136",
      "r137"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RelatedPartyDomain": {
     "auth_ref": [
      "r303"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Related parties include affiliates; other entities for which investments are accounted for by the equity method by the entity; trusts for benefit of employees; and principal owners, management, and members of immediate families. It also may include other parties with which the entity may control or can significantly influence the management or operating policies of the other to an extent that one of the transacting parties might be prevented from fully pursuing its own separate interests.",
        "label": "Related Party [Domain]"
       }
      }
     },
     "localname": "RelatedPartyDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RelatedPartyTransactionsByRelatedPartyAxis": {
     "auth_ref": [
      "r198",
      "r301",
      "r302",
      "r311",
      "r312",
      "r313",
      "r314",
      "r315",
      "r316",
      "r317",
      "r318",
      "r319",
      "r320",
      "r321",
      "r322"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by type of related party. Related parties include, but not limited to, affiliates; other entities for which investments are accounted for by the equity method by the entity; trusts for benefit of employees; and principal owners, management, and members of immediate families. It also may include other parties with which the entity may control or can significantly influence the management or operating policies of the other to an extent that one of the transacting parties might be prevented from fully pursuing its own separate interests.",
        "label": "Related Party [Axis]"
       }
      }
     },
     "localname": "RelatedPartyTransactionsByRelatedPartyAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_RepaymentsOfLongTermDebt": {
     "auth_ref": [
      "r68"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "order": 13.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInFinancingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The cash outflow for debt initially having maturity due after one year or beyond the normal operating cycle, if longer.",
        "label": "Repayments of Long-term Debt",
        "negatedLabel": "Principal payments on debt obligations"
       }
      }
     },
     "localname": "RepaymentsOfLongTermDebt",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ResearchAndDevelopmentExpensePolicy": {
     "auth_ref": [
      "r84",
      "r223"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RestrictedStockMember": {
     "auth_ref": [
      "r104"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Stock including a provision that prohibits sale or substantive sale of an equity instrument for a specified period of time or until specified performance conditions are met.",
        "label": "Restricted Stock [Member]",
        "terseLabel": "Restricted Stock Awards [Member]"
       }
      }
     },
     "localname": "RestrictedStockMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "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]",
        "verboseLabel": "RSUs [Member]"
       }
      }
     },
     "localname": "RestrictedStockUnitsRSUMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RetainedEarningsAccumulatedDeficit": {
     "auth_ref": [
      "r16",
      "r184",
      "r337"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_RetainedEarningsMember": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax": {
     "auth_ref": [
      "r188",
      "r189"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerMember": {
     "auth_ref": [
      "r115"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerPolicyTextBlock": {
     "auth_ref": [
      "r85",
      "r194"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RevenueRecognitionPolicyTextBlock": {
     "auth_ref": [
      "r85",
      "r86"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability": {
     "auth_ref": [
      "r295",
      "r299"
     ],
     "crdr": "debit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of increase in right-of-use asset obtained in exchange for operating lease liability.",
        "label": "Right-of-Use Asset Obtained in Exchange for Operating Lease Liability",
        "terseLabel": "Right-of-use assets obtained in exchange for lease obligations"
       }
      }
     },
     "localname": "RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable": {
     "auth_ref": [
      "r242"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock": {
     "auth_ref": [
      "r105"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Tabular disclosure of an entity's basic and diluted earnings per share calculations, including a reconciliation of numerators and denominators of the basic and diluted per-share computations for income from continuing operations.",
        "label": "Schedule of Earnings Per Share, Basic and Diluted [Table Text Block]",
        "terseLabel": "Basic and Diluted Net Income Per Share"
       }
      }
     },
     "localname": "ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable": {
     "auth_ref": [
      "r98",
      "r100",
      "r103",
      "r107"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock": {
     "auth_ref": [
      "r98",
      "r100",
      "r103",
      "r107"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Tabular disclosure of the effect of income (loss) on basic earnings per share.",
        "label": "Schedule of Earnings Per Share, Basic, by Common Class, Including Two Class Method [Table Text Block]",
        "terseLabel": "Basic Net Income (Loss) per Share"
       }
      }
     },
     "localname": "ScheduleOfEarningsPerShareBasicByCommonClassTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable": {
     "auth_ref": [
      "r202",
      "r214",
      "r220"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock": {
     "auth_ref": [
      "r202",
      "r214",
      "r220"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock": {
     "auth_ref": [
      "r285"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Tabular disclosure of future minimum lease payments as of the date of the latest balance sheet presented, in aggregate and for each of the five years succeeding fiscal years, with separate deductions from the total for the amount representing executor costs, including any profit thereon, included in the minimum lease payments and for the amount of the imputed interest necessary to reduce the net minimum lease payments to present value.",
        "label": "Schedule of Future Minimum Lease Payments for Capital Leases [Table Text Block]",
        "terseLabel": "Future Minimum Payments Under Operating Leases"
       }
      }
     },
     "localname": "ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/OperatingLeasesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable": {
     "auth_ref": [
      "r121",
      "r125",
      "r126",
      "r127",
      "r168"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "A table disclosing the profit or loss and total assets for each reportable segment of the entity. An entity discloses certain information on each reportable segment if the amounts (a) are included in the measure of segment profit or loss reviewed by the chief operating decision maker or (b) are otherwise regularly provided to the chief operating decision maker, even if not included in that measure of segment profit or loss.",
        "label": "Schedule of Segment Reporting Information, by Segment [Table]"
       }
      }
     },
     "localname": "ScheduleOfSegmentReportingInformationBySegmentTable",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock": {
     "auth_ref": [
      "r121",
      "r125",
      "r126",
      "r127",
      "r168"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Tabular disclosure of the profit or loss and total assets for each reportable segment. An entity discloses certain information on each reportable segment if the amounts (a) are included in the measure of segment profit or loss reviewed by the chief operating decision maker or (b) are otherwise regularly provided to the chief operating decision maker, even if not included in that measure of segment profit or loss.",
        "label": "Schedule of Segment Reporting Information, by Segment [Table Text Block]",
        "terseLabel": "Segment Information"
       }
      }
     },
     "localname": "ScheduleOfSegmentReportingInformationBySegmentTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable": {
     "auth_ref": [
      "r203",
      "r217"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock": {
     "auth_ref": [
      "r208"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock": {
     "auth_ref": [
      "r208"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock": {
     "auth_ref": [
      "r148"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock": {
     "auth_ref": [
      "r113",
      "r115",
      "r116",
      "r117",
      "r274",
      "r276"
     ],
     "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]",
        "terseLabel": "Revenue from Collaborative Relationship"
       }
      }
     },
     "localname": "SchedulesOfConcentrationOfRiskByRiskFactorTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SegmentDomain": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Components of an entity that engage in business activities from which they may earn revenue and incur expenses, including transactions with other components of the same entity.",
        "label": "Segments [Domain]"
       }
      }
     },
     "localname": "SegmentDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_SegmentReportingAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Segment Information [Abstract]"
       }
      }
     },
     "localname": "SegmentReportingAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "Segment Reporting, Disclosure of Other Information about Entity's Reportable Segments [Abstract]",
        "terseLabel": "Segment Information [Abstract]"
       }
      }
     },
     "localname": "SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_SegmentReportingDisclosureTextBlock": {
     "auth_ref": [
      "r132"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "The entire disclosure for reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.",
        "label": "Segment Reporting Disclosure [Text Block]",
        "terseLabel": "Segment Information"
       }
      }
     },
     "localname": "SegmentReportingDisclosureTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformation"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SegmentReportingInformationLineItems": {
     "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": "Segment Reporting Information [Line Items]"
       }
      }
     },
     "localname": "SegmentReportingInformationLineItems",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_SegmentReportingPolicyPolicyTextBlock": {
     "auth_ref": [
      "r84"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SellingGeneralAndAdministrativeExpense": {
     "auth_ref": [
      "r57",
      "r163"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_SellingGeneralAndAdministrativeExpensesMember": {
     "auth_ref": [
      "r61"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Primary financial statement caption encompassing selling, general and administrative expense.",
        "label": "Selling, General and Administrative Expenses [Member]",
        "terseLabel": "Selling, General and Administrative [Member]"
       }
      }
     },
     "localname": "SellingGeneralAndAdministrativeExpensesMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensation": {
     "auth_ref": [
      "r75"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited": {
       "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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": "Amendment to Equity Plan [Abstract]"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1": {
     "auth_ref": [
      "r204"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate": {
     "auth_ref": [
      "r211"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate": {
     "auth_ref": [
      "r212"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate": {
     "auth_ref": [
      "r210"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue": {
     "auth_ref": [
      "r207"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain": {
     "auth_ref": [
      "r201",
      "r205"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Award under share-based payment arrangement.",
        "label": "Equity Award [Domain]"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy": {
     "auth_ref": [
      "r84",
      "r203",
      "r206"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1": {
     "auth_ref": [
      "r209",
      "r219"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_SharesIssued": {
     "auth_ref": [
      "r183"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "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 share-based awards and exercise of employee stock options (in shares)"
       }
      }
     },
     "localname": "SharesPaidForTaxWithholdingForShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_SignificantAccountingPoliciesTextBlock": {
     "auth_ref": [
      "r91"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_StatementBusinessSegmentsAxis": {
     "auth_ref": [
      "r0",
      "r125",
      "r168",
      "r178",
      "r179",
      "r180",
      "r343"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by business segments.",
        "label": "Segments [Axis]"
       }
      }
     },
     "localname": "StatementBusinessSegmentsAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SegmentInformationDetails",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementClassOfStockAxis": {
     "auth_ref": [
      "r12",
      "r13",
      "r14",
      "r183"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by the different classes of stock of the entity.",
        "label": "Class of Stock [Axis]"
       }
      }
     },
     "localname": "StatementClassOfStockAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementEquityComponentsAxis": {
     "auth_ref": [
      "r31",
      "r183"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by component of equity.",
        "label": "Equity Components [Axis]"
       }
      }
     },
     "localname": "StatementEquityComponentsAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfCashFlowsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited) [Abstract]"
       }
      }
     },
     "localname": "StatementOfCashFlowsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfFinancialPositionAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) [Abstract]"
       }
      }
     },
     "localname": "StatementOfFinancialPositionAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]"
       }
      }
     },
     "localname": "StatementOfIncomeAndComprehensiveIncomeAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfStockholdersEquityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "label": "CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited) [Abstract]"
       }
      }
     },
     "localname": "StatementOfStockholdersEquityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementTable": {
     "auth_ref": [],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StockIssuedDuringPeriodSharesNewIssues": {
     "auth_ref": [
      "r13",
      "r14",
      "r183",
      "r184"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Number of new stock issued during the period.",
        "label": "Stock Issued During Period, Shares, New Issues",
        "verboseLabel": "Biogen stock purchase (in shares)"
       }
      }
     },
     "localname": "StockIssuedDuringPeriodSharesNewIssues",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation": {
     "auth_ref": [
      "r13",
      "r14",
      "r183",
      "r184"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_StockIssuedDuringPeriodValueNewIssues": {
     "auth_ref": [
      "r13",
      "r14",
      "r183",
      "r184"
     ],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Equity impact of the value of new stock issued during the period. Includes shares issued in an initial public offering or a secondary public offering.",
        "label": "Stock Issued During Period, Value, New Issues",
        "verboseLabel": "Biogen stock purchase"
       }
      }
     },
     "localname": "StockIssuedDuringPeriodValueNewIssues",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_StockRepurchaseProgramAuthorizedAmount1": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Amount of stock repurchase plan authorized.",
        "label": "Stock Repurchase Program, Authorized Amount",
        "terseLabel": "Authorized amount of share repurchase program"
       }
      }
     },
     "localname": "StockRepurchaseProgramAuthorizedAmount1",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_StockRepurchasedDuringPeriodShares": {
     "auth_ref": [
      "r13",
      "r14",
      "r183",
      "r184"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Number of shares that have been repurchased during the period and have not been retired and are not held in treasury. Some state laws may govern the circumstances under which an entity may acquire its own stock and prescribe the accounting treatment therefore. This element is used when state law does not recognize treasury stock.",
        "label": "Stock Repurchased During Period, Shares",
        "terseLabel": "Shares repurchased (in shares)"
       }
      }
     },
     "localname": "StockRepurchasedDuringPeriodShares",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_StockholdersEquity": {
     "auth_ref": [
      "r14",
      "r17",
      "r18",
      "r134"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 0.0,
       "parentTag": "us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest",
       "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 Ionis stockholders' equity"
       }
      }
     },
     "localname": "StockholdersEquity",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest": {
     "auth_ref": [
      "r244",
      "r245",
      "r256"
     ],
     "calculation": {
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited": {
       "order": 2.0,
       "parentTag": "us-gaap_LiabilitiesAndStockholdersEquity",
       "weight": 1.0
      }
     },
     "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",
        "totalLabel": "Total stockholders' equity"
       }
      }
     },
     "localname": "StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited",
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_SubsequentEventMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Identifies event that occurred after the balance sheet date but before financial statements are issued or available to be issued.",
        "label": "Subsequent Event [Member]"
       }
      }
     },
     "localname": "SubsequentEventMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_SubsequentEventTypeAxis": {
     "auth_ref": [
      "r304"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Information by event that occurred after the balance sheet date but before financial statements are issued or available to be issued.",
        "label": "Subsequent Event Type [Axis]"
       }
      }
     },
     "localname": "SubsequentEventTypeAxis",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_SubsequentEventTypeDomain": {
     "auth_ref": [
      "r304"
     ],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Event that occurred after the balance sheet date but before financial statements are issued or available to be issued.",
        "label": "Subsequent Event Type [Domain]"
       }
      }
     },
     "localname": "SubsequentEventTypeDomain",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy": {
     "auth_ref": [
      "r138"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain": {
     "auth_ref": [
      "r310"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_TypeOfAdoptionMember": {
     "auth_ref": [],
     "lang": {
      "en-US": {
       "role": {
        "documentation": "Adoption and early adoption of sources of change to generally accepted accounting principles (GAAP) in the United States. The FASB released the FASB Accounting Standards Codification as the authoritative source of literature effective for interim and annual periods ending after September 15, 2009. As part of the Codification process, the FASB issues Accounting Standards Updates to amend the Codification but otherwise the Accounting Standards Updates are not authoritative in their own right. All previous accounting standards (such as FASB Statements of Financial Accounting Standards, FASB Interpretations, FASB Staff Positions, Emerging Issues Task Force Consensuses, other pronouncements of the FASB or other designated bodies, or other forms of GAAP are considered accounting pronouncements) were superseded upon the adoption of the Codification. For an interim period, references to the superseded standards are included to help users transition from the previous accounting hierarchy and will be removed from future versions of this taxonomy.",
        "label": "Type of Adoption [Domain]"
       }
      }
     },
     "localname": "TypeOfAdoptionMember",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_TypeOfArrangementAxis": {
     "auth_ref": [
      "r242"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails",
      "http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables",
      "http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_USGovernmentAgenciesDebtSecuritiesMember": {
     "auth_ref": [
      "r196",
      "r329"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_USStatesAndPoliticalSubdivisionsMember": {
     "auth_ref": [
      "r196",
      "r346"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_USTreasurySecuritiesMember": {
     "auth_ref": [
      "r196",
      "r199",
      "r329"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/FairValueMeasurementsDetails",
      "http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://isispharm.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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/InvestmentsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_UseOfEstimates": {
     "auth_ref": [
      "r109",
      "r110",
      "r111",
      "r112",
      "r118",
      "r119",
      "r120"
     ],
     "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/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding": {
     "auth_ref": [
      "r97",
      "r103"
     ],
     "calculation": {
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "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 income (loss) per share (in shares)",
        "totalLabel": "Shares used in computing diluted net income per share (in shares)"
       }
      }
     },
     "localname": "WeightedAverageNumberOfDilutedSharesOutstanding",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_WeightedAverageNumberOfSharesOutstandingBasic": {
     "auth_ref": [
      "r95",
      "r103"
     ],
     "calculation": {
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding",
       "weight": 1.0
      }
     },
     "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 income (loss) per share (in shares)",
        "terseLabel": "Weighted average shares outstanding (in shares)"
       }
      }
     },
     "localname": "WeightedAverageNumberOfSharesOutstandingBasic",
     "nsuri": "http://fasb.org/us-gaap/2019-01-31",
     "presentation": [
      "http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited",
      "http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails"
     ],
     "xbrltype": "sharesItemType"
    }
   },
   "unitCount": 15
  }
 },
 "std_ref": {
  "r0": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)",
   "Topic": "205",
   "URI": "http://asc.fasb.org/extlink&oid=109222650&loc=d3e1361-107760"
  },
  "r1": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "205",
   "URI": "http://asc.fasb.org/topic&trid=2122149"
  },
  "r10": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r100": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1278-109256"
  },
  "r101": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "60B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=SL5780133-109256"
  },
  "r102": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1337-109256"
  },
  "r103": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=6371337&loc=d3e3550-109257"
  },
  "r104": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=6371337&loc=d3e3550-109257"
  },
  "r105": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=6371337&loc=d3e3550-109257"
  },
  "r106": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=6371337&loc=d3e3630-109257"
  },
  "r107": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "52",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117327953&loc=d3e4984-109258"
  },
  "r108": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "270",
   "URI": "http://asc.fasb.org/extlink&oid=116846552&loc=d3e543-108305"
  },
  "r109": {
   "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"
  },
  "r11": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r110": {
   "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"
  },
  "r111": {
   "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"
  },
  "r112": {
   "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"
  },
  "r113": {
   "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"
  },
  "r114": {
   "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"
  },
  "r115": {
   "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"
  },
  "r116": {
   "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"
  },
  "r117": {
   "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"
  },
  "r118": {
   "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"
  },
  "r119": {
   "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"
  },
  "r12": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(27))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=6877327&loc=d3e13212-122682"
  },
  "r120": {
   "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"
  },
  "r121": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8721-108599"
  },
  "r122": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8736-108599"
  },
  "r123": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8736-108599"
  },
  "r124": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(h)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8736-108599"
  },
  "r125": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8736-108599"
  },
  "r126": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8813-108599"
  },
  "r127": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "30",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8906-108599"
  },
  "r128": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8933-108599"
  },
  "r129": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e8933-108599"
  },
  "r13": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r130": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "40",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e9031-108599"
  },
  "r131": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "42",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=115929826&loc=d3e9054-108599"
  },
  "r132": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "280",
   "URI": "http://asc.fasb.org/topic&trid=2134510"
  },
  "r133": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=118936363&loc=d3e5033-111524"
  },
  "r134": {
   "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=27010918&loc=d3e74512-122707"
  },
  "r135": {
   "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"
  },
  "r136": {
   "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"
  },
  "r137": {
   "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"
  },
  "r138": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "310",
   "URI": "http://asc.fasb.org/topic&trid=2196771"
  },
  "r139": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118954083&loc=d3e26610-111562"
  },
  "r14": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r140": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118954083&loc=d3e26853-111562"
  },
  "r141": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118954083&loc=d3e26626-111562"
  },
  "r142": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27161-111563"
  },
  "r143": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(aa)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27161-111563"
  },
  "r144": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27161-111563"
  },
  "r145": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27161-111563"
  },
  "r146": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27290-111563"
  },
  "r147": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)(3)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27290-111563"
  },
  "r148": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27290-111563"
  },
  "r149": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=118939692&loc=d3e27337-111563"
  },
  "r15": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r150": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "320",
   "URI": "http://asc.fasb.org/topic&trid=2196928"
  },
  "r151": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "321",
   "URI": "http://asc.fasb.org/extlink&oid=116654751&loc=SL75117546-209714"
  },
  "r152": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=119407570&loc=SL82919244-210447"
  },
  "r153": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=119407570&loc=SL82919249-210447"
  },
  "r154": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=119407570&loc=SL82919253-210447"
  },
  "r155": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=119407570&loc=SL82919258-210447"
  },
  "r156": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=119407570&loc=SL82919230-210447"
  },
  "r157": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=118942338&loc=SL82898722-210454"
  },
  "r158": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=118955579&loc=SL82922888-210455"
  },
  "r159": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=118955579&loc=SL82922888-210455"
  },
  "r16": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r160": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=118955579&loc=SL82922895-210455"
  },
  "r161": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=118955579&loc=SL82922900-210455"
  },
  "r162": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=118942371&loc=SL82922954-210456"
  },
  "r163": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "30",
   "SubTopic": "10",
   "Topic": "330",
   "URI": "http://asc.fasb.org/extlink&oid=68048583&loc=d3e3636-108311"
  },
  "r164": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "35",
   "SubTopic": "10",
   "Topic": "330",
   "URI": "http://asc.fasb.org/extlink&oid=116846819&loc=d3e3927-108312"
  },
  "r165": {
   "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"
  },
  "r166": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "330",
   "URI": "http://asc.fasb.org/extlink&oid=116847112&loc=d3e4542-108314"
  },
  "r167": {
   "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"
  },
  "r168": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "350",
   "URI": "http://asc.fasb.org/extlink&oid=108376223&loc=d3e13816-109267"
  },
  "r169": {
   "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"
  },
  "r17": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r170": {
   "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"
  },
  "r171": {
   "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"
  },
  "r172": {
   "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"
  },
  "r173": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=109226348&loc=d3e2420-110228"
  },
  "r174": {
   "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"
  },
  "r175": {
   "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"
  },
  "r176": {
   "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"
  },
  "r177": {
   "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"
  },
  "r178": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=109226691&loc=d3e2941-110230"
  },
  "r179": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "420",
   "URI": "http://asc.fasb.org/extlink&oid=6394359&loc=d3e17939-110869"
  },
  "r18": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r180": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB Topic 5.P.4(d))",
   "Topic": "420",
   "URI": "http://asc.fasb.org/extlink&oid=115931487&loc=d3e140904-122747"
  },
  "r181": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "450",
   "URI": "http://asc.fasb.org/extlink&oid=118942415&loc=d3e14615-108349"
  },
  "r182": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=6802200&loc=d3e1835-112601"
  },
  "r183": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=109259400&loc=d3e21463-112644"
  },
  "r184": {
   "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=27012166&loc=d3e187085-122770"
  },
  "r185": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118944033&loc=SL49130531-203044"
  },
  "r186": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118944033&loc=SL49130532-203044"
  },
  "r187": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118944033&loc=SL49130533-203044"
  },
  "r188": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118956577&loc=SL49130543-203045"
  },
  "r189": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118956577&loc=SL49130545-203045"
  },
  "r19": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r190": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118956577&loc=SL49130549-203045"
  },
  "r191": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118956577&loc=SL49130549-203045"
  },
  "r192": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118944142&loc=SL49130690-203046-203046"
  },
  "r193": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=118944142&loc=SL49130690-203046-203046"
  },
  "r194": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "606",
   "URI": "http://asc.fasb.org/topic&trid=49130388"
  },
  "r195": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "705",
   "URI": "http://asc.fasb.org/topic&trid=2122478"
  },
  "r196": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(ii)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=118255775&loc=d3e1928-114920"
  },
  "r197": {
   "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=118255775&loc=d3e1928-114920"
  },
  "r198": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(n)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=118255775&loc=d3e1928-114920"
  },
  "r199": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=118257860&loc=d3e4179-114921"
  },
  "r2": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=118951113&loc=d3e6676-107765"
  },
  "r20": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r200": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "35",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116855982&loc=d3e4534-113899"
  },
  "r201": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5047-113901"
  },
  "r202": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5047-113901"
  },
  "r203": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5047-113901"
  },
  "r204": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r205": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a),(g)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r206": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b),(f)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r207": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r208": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r209": {
   "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=116856206&loc=d3e5070-113901"
  },
  "r21": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r210": {
   "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=116856206&loc=d3e5070-113901"
  },
  "r211": {
   "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=116856206&loc=d3e5070-113901"
  },
  "r212": {
   "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=116856206&loc=d3e5070-113901"
  },
  "r213": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(g)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r214": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(h)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r215": {
   "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=116856206&loc=d3e5070-113901"
  },
  "r216": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(i)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r217": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=d3e5070-113901"
  },
  "r218": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=116856206&loc=SL79508275-113901"
  },
  "r219": {
   "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=115993241&loc=d3e301413-122809"
  },
  "r22": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r220": {
   "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=115993241&loc=d3e301413-122809"
  },
  "r221": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=118258462&loc=d3e11149-113907"
  },
  "r222": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=118258462&loc=d3e11178-113907"
  },
  "r223": {
   "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"
  },
  "r224": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=116821951&loc=d3e32247-109318"
  },
  "r225": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=116821951&loc=d3e32280-109318"
  },
  "r226": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=116821951&loc=d3e31917-109318"
  },
  "r227": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=116821951&loc=d3e31931-109318"
  },
  "r228": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32687-109319"
  },
  "r229": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32698-109319"
  },
  "r23": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r230": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32809-109319"
  },
  "r231": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "19",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32840-109319"
  },
  "r232": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32537-109319"
  },
  "r233": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32847-109319"
  },
  "r234": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=84230637&loc=d3e32639-109319"
  },
  "r235": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB TOPIC 6.I)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=116825942&loc=d3e330036-122817"
  },
  "r236": {
   "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=116825942&loc=d3e330036-122817"
  },
  "r237": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=109238882&loc=d3e38679-109324"
  },
  "r238": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "05",
   "SubTopic": "30",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=65884525&loc=d3e40913-109327"
  },
  "r239": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "740",
   "URI": "http://asc.fasb.org/topic&trid=2144680"
  },
  "r24": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r240": {
   "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"
  },
  "r241": {
   "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"
  },
  "r242": {
   "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"
  },
  "r243": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "808",
   "URI": "http://asc.fasb.org/topic&trid=5833765"
  },
  "r244": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=108774443&loc=SL4568447-111683"
  },
  "r245": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=108774443&loc=SL4568740-111683"
  },
  "r246": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "19",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=108774443&loc=SL4569616-111683"
  },
  "r247": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=108774443&loc=SL4569643-111683"
  },
  "r248": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=108774443&loc=SL4613674-111683"
  },
  "r249": {
   "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"
  },
  "r25": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r250": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(1)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=SL4573702-111684"
  },
  "r251": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(2)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=SL4573702-111684"
  },
  "r252": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)(1)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=SL4573702-111684"
  },
  "r253": {
   "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"
  },
  "r254": {
   "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"
  },
  "r255": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=SL4573702-111684"
  },
  "r256": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4I",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116874947&loc=SL4590271-111686"
  },
  "r257": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4J",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116874947&loc=SL4591551-111686"
  },
  "r258": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4K",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116874947&loc=SL4591552-111686"
  },
  "r259": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.3A-02)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116822174&loc=d3e355033-122828"
  },
  "r26": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r260": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.3A-03)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116822174&loc=d3e355100-122828"
  },
  "r261": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.3A-04)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116822174&loc=d3e355119-122828"
  },
  "r262": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "810",
   "URI": "http://asc.fasb.org/topic&trid=2197479"
  },
  "r263": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=109980867&loc=SL5618551-113959"
  },
  "r264": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=109980867&loc=SL5624163-113959"
  },
  "r265": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19207-110258"
  },
  "r266": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19207-110258"
  },
  "r267": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bb)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19207-110258"
  },
  "r268": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bbb)(1)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19207-110258"
  },
  "r269": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bbb)(2)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19207-110258"
  },
  "r27": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r270": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19207-110258"
  },
  "r271": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=d3e19279-110258"
  },
  "r272": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=117815213&loc=SL6742756-110258"
  },
  "r273": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=99377092&loc=SL75136599-209740"
  },
  "r274": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=118260190&loc=d3e13531-108611"
  },
  "r275": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=118260190&loc=d3e13537-108611"
  },
  "r276": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=118260190&loc=d3e13537-108611"
  },
  "r277": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "230",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=98513438&loc=d3e33268-110906"
  },
  "r278": {
   "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"
  },
  "r279": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32157-110900"
  },
  "r28": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r280": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32211-110900"
  },
  "r281": {
   "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"
  },
  "r282": {
   "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"
  },
  "r283": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=114775744&loc=d3e28541-108399"
  },
  "r284": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=114775744&loc=d3e28555-108399"
  },
  "r285": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(b)",
   "Topic": "840",
   "URI": "http://asc.fasb.org/extlink&oid=84164817&loc=d3e45280-112737"
  },
  "r286": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=119364159&loc=SL77916155-209984"
  },
  "r287": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888419&loc=SL77918627-209977"
  },
  "r288": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888419&loc=SL77918627-209977"
  },
  "r289": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888419&loc=SL77918638-209977"
  },
  "r29": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r290": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888419&loc=SL77918643-209977"
  },
  "r291": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918666-209980"
  },
  "r292": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)(3)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918673-209980"
  },
  "r293": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918673-209980"
  },
  "r294": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(g)(1)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918686-209980"
  },
  "r295": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(g)(2)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918686-209980"
  },
  "r296": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(g)(3)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918686-209980"
  },
  "r297": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(g)(4)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918686-209980"
  },
  "r298": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888426&loc=SL77918701-209980"
  },
  "r299": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "53",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=77888399&loc=SL77918982-209971"
  },
  "r3": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=118951113&loc=d3e6676-107765"
  },
  "r30": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r300": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "SubTopic": "20",
   "Topic": "842",
   "URI": "http://asc.fasb.org/subtopic&trid=77888251"
  },
  "r301": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "850",
   "URI": "http://asc.fasb.org/extlink&oid=6457730&loc=d3e39549-107864"
  },
  "r302": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "850",
   "URI": "http://asc.fasb.org/extlink&oid=6457730&loc=d3e39603-107864"
  },
  "r303": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "850",
   "URI": "http://asc.fasb.org/topic&trid=2122745"
  },
  "r304": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "855",
   "URI": "http://asc.fasb.org/extlink&oid=6842918&loc=SL6314017-165662"
  },
  "r305": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "855",
   "URI": "http://asc.fasb.org/extlink&oid=6842918&loc=SL6314020-165662"
  },
  "r306": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=118948506&loc=d3e107207-111719"
  },
  "r307": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=118948506&loc=d3e107207-111719"
  },
  "r308": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=118948506&loc=d3e107207-111719"
  },
  "r309": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=118948506&loc=d3e107207-111719"
  },
  "r31": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r310": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=116651436&loc=d3e122625-111746"
  },
  "r311": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(a)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e61929-109447"
  },
  "r312": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(b)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e61929-109447"
  },
  "r313": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(a)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e62059-109447"
  },
  "r314": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(b)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e62059-109447"
  },
  "r315": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(a)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e62395-109447"
  },
  "r316": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(b)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e62395-109447"
  },
  "r317": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "33",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(a)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e62479-109447"
  },
  "r318": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "33",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(b)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e62479-109447"
  },
  "r319": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "35A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(a)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=SL6807758-109447"
  },
  "r32": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r320": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "35A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(b)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=SL6807758-109447"
  },
  "r321": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(c)(1)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e61872-109447"
  },
  "r322": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "235",
   "Subparagraph": "(c)(2)",
   "Topic": "932",
   "URI": "http://asc.fasb.org/extlink&oid=68064819&loc=d3e61872-109447"
  },
  "r323": {
   "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=6876686&loc=d3e534808-122878"
  },
  "r324": {
   "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=6876686&loc=d3e534808-122878"
  },
  "r325": {
   "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=6876686&loc=d3e534808-122878"
  },
  "r326": {
   "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=6876686&loc=d3e534808-122878"
  },
  "r327": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(22))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=6876686&loc=d3e534808-122878"
  },
  "r328": {
   "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=6876686&loc=d3e534808-122878"
  },
  "r329": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(6)(a)(1))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=6876686&loc=d3e534808-122878"
  },
  "r33": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r330": {
   "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=116637391&loc=SL114874048-224260"
  },
  "r331": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.9-04(23))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=116637391&loc=SL114874048-224260"
  },
  "r332": {
   "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=116637391&loc=SL114874048-224260"
  },
  "r333": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r334": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r335": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r336": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r337": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r338": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(24))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=119400593&loc=d3e572229-122910"
  },
  "r339": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r34": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r340": {
   "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=119400593&loc=d3e572229-122910"
  },
  "r341": {
   "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=116637232&loc=SL114874131-224263"
  },
  "r342": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(19))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=116637232&loc=SL114874131-224263"
  },
  "r343": {
   "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"
  },
  "r344": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13H",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "40",
   "Subparagraph": "(a)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=117419784&loc=SL117783719-158441"
  },
  "r345": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13H",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "40",
   "Subparagraph": "(c)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=117419784&loc=SL117783719-158441"
  },
  "r346": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "80",
   "Subparagraph": "(e)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=117420044&loc=d3e19393-158473"
  },
  "r347": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "825",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=99380617&loc=SL75241803-196195"
  },
  "r348": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12(2)(i))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611133-123010"
  },
  "r349": {
   "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=50485924&loc=d3e611133-123010"
  },
  "r35": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r350": {
   "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=50485924&loc=d3e611133-123010"
  },
  "r351": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12C(1)(a))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611225-123010"
  },
  "r352": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12C(1)(b))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611225-123010"
  },
  "r353": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12C(2))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611225-123010"
  },
  "r354": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12C)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611225-123010"
  },
  "r355": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12C.1(b),2)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611225-123010"
  },
  "r356": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12C(2))-",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611225-123010"
  },
  "r357": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-13(1))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611282-123010"
  },
  "r358": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-13)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611282-123010"
  },
  "r359": {
   "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=50485924&loc=d3e611322-123010"
  },
  "r36": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r360": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-15(Column A))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=50485924&loc=d3e611379-123010"
  },
  "r361": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "740",
   "Topic": "954",
   "URI": "http://asc.fasb.org/extlink&oid=6491622&loc=d3e9504-115650"
  },
  "r362": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "360",
   "Subparagraph": "(SX 210.12-28(Footnote 4))",
   "Topic": "970",
   "URI": "http://asc.fasb.org/extlink&oid=6590653&loc=d3e638233-123024"
  },
  "r363": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "b"
  },
  "r364": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "d1-1"
  },
  "r365": {
   "Name": "Form 10-Q",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "13",
   "Subsection": "a-13"
  },
  "r366": {
   "Name": "Forms 10-K, 10-Q, 20-F",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "13",
   "Subsection": "a-1-"
  },
  "r367": {
   "Name": "Regulation 12B",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "b-2"
  },
  "r368": {
   "Name": "Regulation S-T",
   "Number": "232",
   "Publisher": "SEC",
   "Section": "405"
  },
  "r369": {
   "Article": "6",
   "Name": "Regulation S-X (SX)",
   "Number": "210",
   "Paragraph": "(c)",
   "Publisher": "SEC",
   "Section": "10",
   "Subparagraph": "(1)"
  },
  "r37": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a-c)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669646-108580"
  },
  "r38": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669646-108580"
  },
  "r39": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669646-108580"
  },
  "r4": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=118951113&loc=d3e6676-107765"
  },
  "r40": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=d3e637-108580"
  },
  "r41": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=d3e681-108580"
  },
  "r42": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669686-108580"
  },
  "r43": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL34724394-108580"
  },
  "r44": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669619-108580"
  },
  "r45": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669619-108580"
  },
  "r46": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669625-108580"
  },
  "r47": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=SL7669625-108580"
  },
  "r48": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=118930883&loc=d3e557-108580"
  },
  "r49": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=116657188&loc=SL116659661-227067"
  },
  "r5": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=118951113&loc=d3e6801-107765"
  },
  "r50": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r51": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r52": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03(21))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=116634182&loc=SL114868664-224227"
  },
  "r53": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r54": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r55": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.19)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=116634182&loc=SL114868664-224227"
  },
  "r56": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r57": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r58": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r59": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r6": {
   "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"
  },
  "r60": {
   "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=116634182&loc=SL114868664-224227"
  },
  "r61": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=116634182&loc=SL114868664-224227"
  },
  "r62": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3151-108585"
  },
  "r63": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3179-108585"
  },
  "r64": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3213-108585"
  },
  "r65": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3213-108585"
  },
  "r66": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3255-108585"
  },
  "r67": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3291-108585"
  },
  "r68": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3291-108585"
  },
  "r69": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3367-108585"
  },
  "r7": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r70": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3000-108585"
  },
  "r71": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "24",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3521-108585"
  },
  "r72": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3536-108585"
  },
  "r73": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3536-108585"
  },
  "r74": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3536-108585"
  },
  "r75": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3602-108585"
  },
  "r76": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3602-108585"
  },
  "r77": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3602-108585"
  },
  "r78": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=118932676&loc=d3e3044-108585"
  },
  "r79": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=98513485&loc=d3e4297-108586"
  },
  "r8": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r80": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=98513485&loc=d3e4304-108586"
  },
  "r81": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=98513485&loc=d3e4313-108586"
  },
  "r82": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=98513485&loc=d3e4332-108586"
  },
  "r83": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=98513485&loc=SL98516268-108586"
  },
  "r84": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=84158767&loc=d3e18780-107790"
  },
  "r85": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=84158767&loc=d3e18823-107790"
  },
  "r86": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=84158767&loc=d3e18823-107790"
  },
  "r87": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(a))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=26873400&loc=d3e23780-122690"
  },
  "r88": {
   "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=26873400&loc=d3e23780-122690"
  },
  "r89": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08.(h)(1)(i))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=26873400&loc=d3e23780-122690"
  },
  "r9": {
   "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=6877327&loc=d3e13212-122682"
  },
  "r90": {
   "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=26873400&loc=d3e23780-122690"
  },
  "r91": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "235",
   "URI": "http://asc.fasb.org/topic&trid=2122369"
  },
  "r92": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=109234566&loc=d3e22499-107794"
  },
  "r93": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=109234566&loc=d3e22694-107794"
  },
  "r94": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=109234566&loc=d3e22583-107794"
  },
  "r95": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1448-109256"
  },
  "r96": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1377-109256"
  },
  "r97": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1505-109256"
  },
  "r98": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1252-109256"
  },
  "r99": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=117326831&loc=d3e1500-109256"
  }
 },
 "version": "2.1"
}
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>30
<FILENAME>R49.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6830778640">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Segment</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th"><div>Apr. 30, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NumberOfReportableSegments', window );">Number of reportable segments | Segment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">165,369<span></span>
</td>
<td class="nump">163,967<span></span>
</td>
<td class="nump">523,689<span></span>
</td>
<td class="nump">479,716<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">2,523<span></span>
</td>
<td class="num">(18,572)<span></span>
</td>
<td class="nump">105,229<span></span>
</td>
<td class="num">(72,157)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="nump">2,894,989<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,894,989<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,667,784<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CommercialMember', window );">Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">95,699<span></span>
</td>
<td class="nump">82,756<span></span>
</td>
<td class="nump">252,085<span></span>
</td>
<td class="nump">181,975<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SPINRAZARoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">81,672<span></span>
</td>
<td class="nump">70,010<span></span>
</td>
<td class="nump">211,884<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">Product Sales, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">11,945<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">28,563<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">2,082<span></span>
</td>
<td class="nump">12,746<span></span>
</td>
<td class="nump">11,638<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue Under Collaborative Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 72,193<span></span>
</td>
<td class="nump">62,639<span></span>
</td>
<td class="nump">$ 376,833<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">75.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">76.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 152,783<span></span>
</td>
<td class="nump">178,061<span></span>
</td>
<td class="nump">$ 514,862<span></span>
</td>
<td class="nump">410,025<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">119,147<span></span>
</td>
<td class="nump">87,664<span></span>
</td>
<td class="nump">355,437<span></span>
</td>
<td class="nump">279,084<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">33,636<span></span>
</td>
<td class="nump">90,397<span></span>
</td>
<td class="nump">159,425<span></span>
</td>
<td class="nump">130,941<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="nump">3,233,175<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,233,175<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,975,491<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">83,618<span></span>
</td>
<td class="nump">77,956<span></span>
</td>
<td class="nump">220,350<span></span>
</td>
<td class="nump">177,175<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">81,672<span></span>
</td>
<td class="nump">70,010<span></span>
</td>
<td class="nump">211,884<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | Product Sales, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">1,946<span></span>
</td>
<td class="nump">7,946<span></span>
</td>
<td class="nump">8,466<span></span>
</td>
<td class="nump">9,432<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Ionis Core [Member] | R&amp;D Revenue Under Collaborative Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">69,165<span></span>
</td>
<td class="nump">100,105<span></span>
</td>
<td class="nump">294,512<span></span>
</td>
<td class="nump">232,850<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">20,624<span></span>
</td>
<td class="nump">19,241<span></span>
</td>
<td class="nump">211,063<span></span>
</td>
<td class="nump">54,670<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">53,215<span></span>
</td>
<td class="nump">84,249<span></span>
</td>
<td class="nump">256,152<span></span>
</td>
<td class="nump">213,428<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="num">(32,591)<span></span>
</td>
<td class="num">(65,008)<span></span>
</td>
<td class="num">(45,089)<span></span>
</td>
<td class="num">(158,758)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="nump">383,167<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">383,167<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">365,261<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">12,081<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="nump">34,735<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | Product Sales, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">11,945<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">28,563<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">136<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="nump">6,172<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember', window );">Operating Segments [Member] | Akcea Therapeutics [Member] | R&amp;D Revenue Under Collaborative Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">8,543<span></span>
</td>
<td class="nump">7,241<span></span>
</td>
<td class="nump">176,328<span></span>
</td>
<td class="nump">42,670<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="num">(5,515)<span></span>
</td>
<td class="num">(51,907)<span></span>
</td>
<td class="num">(97,007)<span></span>
</td>
<td class="num">(57,136)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="num">(6,993)<span></span>
</td>
<td class="num">(7,946)<span></span>
</td>
<td class="num">(87,900)<span></span>
</td>
<td class="num">(12,796)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">1,478<span></span>
</td>
<td class="num">(43,961)<span></span>
</td>
<td class="num">(9,107)<span></span>
</td>
<td class="num">(44,340)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets as of current period</a></td>
<td class="num">(721,353)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(721,353)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (672,968)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,200)<span></span>
</td>
<td class="num">(3,000)<span></span>
</td>
<td class="num">(7,200)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | Product Sales, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | Licensing and Other Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,200)<span></span>
</td>
<td class="num">(3,000)<span></span>
</td>
<td class="num">(7,200)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember', window );">Elimination of Intercompany Activity [Member] | R&amp;D Revenue Under Collaborative Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="num">$ (5,515)<span></span>
</td>
<td class="num">$ (44,707)<span></span>
</td>
<td class="num">$ (94,007)<span></span>
</td>
<td class="num">$ (49,936)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_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=6876686&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 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<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)(12))<br> -URI http://asc.fasb.org/extlink&amp;oid=119400593&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_Assets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&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_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NumberOfReportableSegments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of segments reported by the entity. A reportable segment is a component of an entity for which there is an accounting requirement to report separate financial information on that component in the entity's financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfReportableSegments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_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>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingAbstract</td>
</tr>
<tr>
<td style="padding-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_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>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_SegmentReportingDisclosureOfOtherInformationAboutEntitysReportableSegmentsAbstract</td>
</tr>
<tr>
<td style="padding-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_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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidationItemsAxis=us-gaap_OperatingSegmentsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementBusinessSegmentsAxis=ions_AkceaTherapeuticsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementBusinessSegmentsAxis=ions_AkceaTherapeuticsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidationItemsAxis=us-gaap_IntersegmentEliminationMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>31
<FILENAME>R41.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6808138768">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Operating Leases (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Option</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 13,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">$ 17,731<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 17,731<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1', window );">Weighted average remaining lease term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">8 years 3 months 18 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">8 years 3 months 18 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent', window );">Weighted average discount rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeasePayments', window );">Operating lease cash payments</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract', window );"><strong>Annual Future Minimum Payments Under Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths', window );">Remainder of 2019</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">801<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">801<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo', window );">2020</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,282<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,282<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree', window );">2021</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,019<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,019<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour', window );">2022</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,781<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,781<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive', window );">2023</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,520<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,520<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive', window );">Thereafter</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">11,861<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11,861<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Total minimum lease payments</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">24,264<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">24,264<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount', window );">Imputed interest</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(6,533)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(6,533)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Total operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">17,731<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">17,731<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseExpense', window );">Rent expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 800<span></span>
</td>
<td class="nump">$ 1,000<span></span>
</td>
<td class="nump">$ 2,700<span></span>
</td>
<td class="nump">$ 1,800<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember', window );">Office and Laboratory Space Adjacent to Manufacturing Facility [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember', window );">Office Space Subleased to Akcea [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Office Space for Corporate Headquarters [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Term of lease</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">123 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">123 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeOperatingLeaseAllowanceForTenantImprovements', window );">Tenant improvement allowance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 3,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation', window );">Initial amount of letter of credit</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate', window );">Letter of credit on third anniversary of rent commencement date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate', window );">Letter of credit on fifth anniversary of rent commencement date</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,200<span></span>
</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 deposits and other assets 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">Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating leasing arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseAllowanceForTenantImprovements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Allowance for tenant improvements to the office space included in the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseAllowanceForTenantImprovements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Initial letter of credit provided to lessor to secure lease obligation under lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the fifth anniversary of the rent commencement date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Letter of credit provided to lessor to secure lease obligation under lessee's operating lease on the third anniversary of the rent commencement date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeasePeriodOfFreeRent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due after fifth fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in next fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in fifth fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in fourth fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in third fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments for operating lease, due in second fiscal year following latest fiscal year.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments in excess of discounted obligation for lease payments for operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseRenewalTerm</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of operating lease expense. Excludes sublease income.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 4<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918638-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeasePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow from operating lease, excluding payments to bring another asset to condition and location necessary for its intended use.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 5<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918643-209977<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeasePayments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's right to use underlying asset under operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Weighted average discount rate for operating lease calculated at point in time.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=77888399&amp;loc=SL77918982-209971<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining lease term for operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI http://asc.fasb.org/extlink&amp;oid=77888399&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888426&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceForCorporateHeadquartersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_OfficeSpaceForCorporateHeadquartersMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>R45.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6807732944">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, GSK (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Drug</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Drug</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 72,193<span></span>
</td>
<td class="nump">$ 62,639<span></span>
</td>
<td class="nump">$ 376,833<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfDrugsCurrentlyBeingAdvanced', window );">Number of drugs being advanced | Drug</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">15.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 164,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 164,000<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | License Fees [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 25,100<span></span>
</td>
<td class="nump">$ 100<span></span>
</td>
<td class="nump">$ 25,300<span></span>
</td>
<td class="nump">$ 1,500<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_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 milestone 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_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_NumberOfDrugsCurrentlyBeingAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 drugs currently being advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfDrugsCurrentlyBeingAdvanced</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://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 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=118260190&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 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118260190&amp;loc=d3e13537-108611<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 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118944033&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=118956577&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=118944033&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 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=us-gaap_LicenseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_LicenseMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6991563824">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation (Details) - Akcea [Member] - shares<br> shares in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
<th class="th"><div>Apr. 30, 2018</div></th>
<th class="th"><div>Jul. 31, 2017</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">76.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">75.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="nump">100.00%<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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Forecast [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="nump">6.9<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>
<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_ReceiptOfSharesInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ReceiptOfSharesInSubsidiary</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
</tr>
<tr>
<td style="padding-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_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_StatementScenarioAxis=srt_ScenarioForecastMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_StatementScenarioAxis=srt_ScenarioForecastMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>35
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6636359792">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that we regularly measure and carry at fair value. At </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions that extend to the fourth quarter of 2019; as a result, we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> The amount we owned in ProQR did not change from </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The tables below segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</span></div>

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

<table cellpadding="0" cellspacing="0" id="ze035bc9b78a548a8a5fdecd96869b42a" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">202,904</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">202,904</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,296,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,296,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">283,365</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">283,365</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366,272</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366,272</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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 (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;">43,265</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">43,265</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-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></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div><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%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (5)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: 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: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,195,958</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">569,176</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,626,176</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="z210039b332e745bb8548fc2512c58d45" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146,281</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146,281</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (6)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,252,960</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,252,960</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">276,612</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">276,612</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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 (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;">79,942</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">79,942</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-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></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (5)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,017,298</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">406,435</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,609,514</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines on our condensed consolidated balance sheet:</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbee9abbccdd54e73807b84f4e3b2b782" 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.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z438bdc6881aa4cb99b165b8919727dda" 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;">$16.6 million was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4a15bc1d737a430282eea21dc5b0bfb3" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3864b9dae47f4db89495ac682873943c" 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;">$3.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb45245eabfe741ed8a9fa3ca3dc821f5" 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;">Included in other current assets.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd2f62bfc179a4c6ea80ab9be8baa40fe" 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;">$50.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28e1624d992e41cbb67711b300f91fbe" 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;">$14.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</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=117815213&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=117815213&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>36
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6817128320">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Cost of Products Sold (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSoldAbstract', window );"><strong>Cost of Products Sold [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_CostOfProductsSoldPreviouslyRecognized', window );">Previously expensed costs to produce TEGSEDI related to TEGSEDI commercial revenue</a></td>
<td class="nump">$ 0.2<span></span>
</td>
<td class="nump">$ 0.5<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CostOfProductsSoldPreviouslyRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The costs related to goods produced and sold that were previously recognized as expense and are related to the commercial revenue recognized during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CostOfProductsSoldPreviouslyRecognized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_CostOfGoodsAndServicesSoldAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CostOfGoodsAndServicesSoldAbstract</td>
</tr>
<tr>
<td style="padding-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>37
<FILENAME>R39.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6813065312">
<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>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">154<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 486,854<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(480)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">70,246<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(99)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">557,100<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (579)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">104<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 304,705<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(268)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">31,675<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(41)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">336,380<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (309)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities issued by U.S. Government Agencies [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">28<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 102,733<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(156)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">22,974<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(26)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">125,707<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (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_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities issued by the U.S. Treasury [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">9<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 77,918<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(55)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">77,918<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (55)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">13<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 1,498<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Unrealized losses, less than 12 months of temporary impairment</a></td>
<td class="num">(1)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue', window );">Estimated fair value, more than 12 months of temporary impairment</a></td>
<td class="nump">15,597<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">Unrealized losses, more than 12 months of temporary impairment</a></td>
<td class="num">(32)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue', window );">Estimated fair value, total temporary impairment</a></td>
<td class="nump">17,095<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss', window );">Unrealized losses, total temporary impairment</a></td>
<td class="num">$ (33)<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_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<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 investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for twelve months or longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<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 investments in debt and equity securities classified as available-for-sale in a continuous loss position.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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 7<br> -URI http://asc.fasb.org/extlink&amp;oid=118939692&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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities in an unrealized loss position which are categorized neither as held-to-maturity nor trading 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;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<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 investments in debt and equity securities classified as available-for-sale that have been in a continuous loss position for less than twelve months.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for less than twelve months.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This item represents the aggregate fair value of investments in debt and equity securities categorized neither as held-to-maturity nor trading securities that have been in a continuous unrealized loss position for twelve months or longer.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of investment positions in available-for-sale investments in a continuous unrealized loss position for which an other-than-temporary impairment (OTTI) has not been recognized in the income statement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (b)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=118939692&amp;loc=d3e27290-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1</td>
</tr>
<tr>
<td style="padding-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_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_CorporateDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>38
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6624003296">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Inventory Valuation (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract', window );"><strong>Inventory Valuation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryWriteDown', window );">Inventory write-off</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">$ 19,375<span></span>
</td>
<td class="nump">$ 8,582<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_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=118951113&amp;loc=d3e6676-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=116846819&amp;loc=d3e3927-108312<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=6877327&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_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_InventoryRawMaterialsAndSuppliesNetOfReservesAbstract</td>
</tr>
<tr>
<td style="padding-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_InventoryWriteDown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of loss from reductions in inventory due to subsequent measurement adjustments, including, but not limited to, physical deterioration, obsolescence, or changes in price levels.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4542-108314<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryWriteDown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>39
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6829595168">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Stock-Based Compensation Expense (Details)<br> $ / shares in Units, $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Officer</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>$ / shares</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2019 </div>
<div>shares</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfExecutiveOfficersTerminatingEmployment', window );">Number of executive officers terminating employment | Officer</a></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 24,126<span></span>
</td>
<td class="nump">$ 34,883<span></span>
</td>
<td class="nump">$ 111,564<span></span>
</td>
<td class="nump">$ 97,210<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.30%<span></span>
</td>
<td class="nump">2.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60.30%<span></span>
</td>
<td class="nump">63.10%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years 7 months 6 days<span></span>
</td>
<td class="text">4 years 7 months 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation expense related to non-vested stock options</a></td>
<td class="nump">143,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 143,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 2 months 12 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember', window );">Board of Director Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
<td class="nump">2.80%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60.70%<span></span>
</td>
<td class="nump">61.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 years 7 months 6 days<span></span>
</td>
<td class="text">6 years 7 months 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.40%<span></span>
</td>
<td class="nump">1.80%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45.60%<span></span>
</td>
<td class="nump">47.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested RSUs</a></td>
<td class="nump">71,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 71,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year 7 months 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Employees [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 59.79<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 64.65<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>Amendment to Equity Plan [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance', window );">Common shares reserved for future issuance (in shares) | shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">23<span></span>
</td>
<td class="nump">16<span></span>
</td>
</tr>
<tr class="rh">
<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 Products Sold [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">127<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 383<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember', window );">Research, Development and Patent [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">23,744<span></span>
</td>
<td class="nump">18,780<span></span>
</td>
<td class="nump">71,935<span></span>
</td>
<td class="nump">57,698<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">255<span></span>
</td>
<td class="nump">$ 16,103<span></span>
</td>
<td class="nump">$ 39,246<span></span>
</td>
<td class="nump">$ 39,512<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="num">$ (19,100)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Employee Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.30%<span></span>
</td>
<td class="nump">2.70%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75.60%<span></span>
</td>
<td class="nump">77.10%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 years 1 month 6 days<span></span>
</td>
<td class="text">6 years 1 month 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Board of Director Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.80%<span></span>
</td>
<td class="nump">2.90%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">73.80%<span></span>
</td>
<td class="nump">78.20%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">6 years 4 months 24 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | ESPP [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.40%<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60.00%<span></span>
</td>
<td class="nump">64.20%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfExecutiveOfficersTerminatingEmployment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of executive officers terminating employment with the company.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfExecutiveOfficersTerminatingEmployment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AllocatedShareBasedCompensationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for award under share-based payment arrangement. Excludes amount capitalized.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&amp;loc=d3e5047-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.F)<br> -URI http://asc.fasb.org/extlink&amp;oid=115993241&amp;loc=d3e301413-122809<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&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_CommonStockCapitalSharesReservedForFutureIssuance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Aggregate number of common shares reserved for future issuance.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.29)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockCapitalSharesReservedForFutureIssuance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract</td>
</tr>
<tr>
<td style="padding-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_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=116856206&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=116856206&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=116856206&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=116856206&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=116856206&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The risk-free interest rate assumption that is used in valuing an option on its own shares.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Rate of weighted-average expected volatility for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=116856206&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=116856206&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2)<br> -URI http://asc.fasb.org/extlink&amp;oid=115993241&amp;loc=d3e301413-122809<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_RelatedPartyTransactionsByRelatedPartyAxis=ions_EmployeeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RelatedPartyTransactionsByRelatedPartyAxis=ions_EmployeeMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_RelatedPartyTransactionsByRelatedPartyAxis=ions_BoardOfDirectorsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RelatedPartyTransactionsByRelatedPartyAxis=ions_BoardOfDirectorsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_ResearchDevelopmentAndPatentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>41
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6828751152">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited) - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid In Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total Ionis Stockholders' Equity [Member]</div></th>
<th class="th"><div>Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</div></th>
<th class="th"><div>Total</div></th>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2017</a></td>
<td class="nump">$ 125<span></span>
</td>
<td class="nump">$ 1,553,681<span></span>
</td>
<td class="num">$ (31,759)<span></span>
</td>
<td class="num">$ (1,241,034)<span></span>
</td>
<td class="nump">$ 281,013<span></span>
</td>
<td class="nump">$ 84,267<span></span>
</td>
<td class="nump">$ 365,280<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2017</a></td>
<td class="nump">124,976<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(46,335)<span></span>
</td>
<td class="num">(46,335)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(46,335)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(834)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(834)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(834)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">61<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">61<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">61<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueNewIssues', window );">Biogen stock purchase</a></td>
<td class="nump">$ 11<span></span>
</td>
<td class="nump">447,954<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">447,965<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">447,965<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues', window );">Biogen stock purchase (in shares)</a></td>
<td class="nump">11,502<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 2<span></span>
</td>
<td class="nump">14,800<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">14,802<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">14,802<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,029<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">97,210<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">97,210<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">97,210<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapetuics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(83,332)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(83,332)<span></span>
</td>
<td class="nump">45,327<span></span>
</td>
<td class="num">(38,005)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2018</a></td>
<td class="nump">$ 138<span></span>
</td>
<td class="nump">2,030,313<span></span>
</td>
<td class="num">(32,532)<span></span>
</td>
<td class="num">(1,287,369)<span></span>
</td>
<td class="nump">710,550<span></span>
</td>
<td class="nump">129,594<span></span>
</td>
<td class="nump">840,144<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2018</a></td>
<td class="nump">137,507<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Jun. 30, 2018</a></td>
<td class="nump">$ 137<span></span>
</td>
<td class="nump">2,011,561<span></span>
</td>
<td class="num">(32,634)<span></span>
</td>
<td class="num">(1,282,810)<span></span>
</td>
<td class="nump">696,254<span></span>
</td>
<td class="nump">121,181<span></span>
</td>
<td class="nump">817,436<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Jun. 30, 2018</a></td>
<td class="nump">137,157<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(4,559)<span></span>
</td>
<td class="num">(4,559)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(4,559)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">133<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">133<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">133<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(31)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(31)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(31)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">6,225<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,226<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,226<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">350<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">34,883<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">34,883<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">34,883<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapetuics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(22,356)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(22,356)<span></span>
</td>
<td class="nump">8,413<span></span>
</td>
<td class="num">(13,943)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2018</a></td>
<td class="nump">$ 138<span></span>
</td>
<td class="nump">2,030,313<span></span>
</td>
<td class="num">(32,532)<span></span>
</td>
<td class="num">(1,287,369)<span></span>
</td>
<td class="nump">710,550<span></span>
</td>
<td class="nump">129,594<span></span>
</td>
<td class="nump">840,144<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2018</a></td>
<td class="nump">137,507<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2018</a></td>
<td class="nump">$ 138<span></span>
</td>
<td class="nump">2,047,250<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
<td class="num">(967,293)<span></span>
</td>
<td class="nump">1,048,079<span></span>
</td>
<td class="nump">139,081<span></span>
</td>
<td class="nump">1,187,160<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2018</a></td>
<td class="nump">137,929<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">109,730<span></span>
</td>
<td class="nump">109,730<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">109,730<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,666<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,666<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,666<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(25)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(25)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(25)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 3<span></span>
</td>
<td class="nump">112,132<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">112,135<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">112,135<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">2,855<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">111,564<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">111,564<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">111,564<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of share-based awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(18,841)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(18,841)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(18,841)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of share-based awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(147)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapetuics, Inc.</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(33,015)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(33,015)<span></span>
</td>
<td class="nump">22,592<span></span>
</td>
<td class="num">(10,423)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2019</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">2,219,090<span></span>
</td>
<td class="num">(25,375)<span></span>
</td>
<td class="num">(857,563)<span></span>
</td>
<td class="nump">1,336,293<span></span>
</td>
<td class="nump">161,673<span></span>
</td>
<td class="nump">1,497,966<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2019</a></td>
<td class="nump">140,637<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Jun. 30, 2019</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">2,177,222<span></span>
</td>
<td class="num">(24,252)<span></span>
</td>
<td class="num">(883,726)<span></span>
</td>
<td class="nump">1,269,384<span></span>
</td>
<td class="nump">187,818<span></span>
</td>
<td class="nump">1,457,202<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Jun. 30, 2019</a></td>
<td class="nump">140,393<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">26,163<span></span>
</td>
<td class="nump">26,163<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">26,163<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,110)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,110)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,110)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">10,130<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">10,131<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">10,131<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">255<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">24,126<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">24,126<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">24,126<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of share-based awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(10,804)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,804)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,804)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of share-based awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(11)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapetuics, Inc.</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">18,416<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">18,416<span></span>
</td>
<td class="num">(26,145)<span></span>
</td>
<td class="num">(7,729)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Sep. 30, 2019</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">$ 2,219,090<span></span>
</td>
<td class="num">$ (25,375)<span></span>
</td>
<td class="num">$ (857,563)<span></span>
</td>
<td class="nump">$ 1,336,293<span></span>
</td>
<td class="nump">$ 161,673<span></span>
</td>
<td class="nump">$ 1,497,966<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Sep. 30, 2019</a></td>
<td class="nump">140,637<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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=118258462&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=116856206&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=118258462&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=116855982&amp;loc=d3e4534-113899<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInStockholdersEquityRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Net Increase or Decrease in balance of noncontrolling interest in the subsidiary during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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=116637391&amp;loc=SL114874048-224260<br><br>Reference 3: 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=118930883&amp;loc=SL7669625-108580<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=116637232&amp;loc=SL114874131-224263<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 S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<br><br>Reference 6: 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=118932676&amp;loc=d3e3602-108585<br><br>Reference 7: 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> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments, of appreciation (loss) in value of unsold available-for-sale securities, attributable to parent entity. Excludes amounts related to other than temporary impairment (OTTI) loss.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<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 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32157-110900<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<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 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 10A<br> -Subparagraph (a-c)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669646-108580<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 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares of stock issued as of the balance sheet date, including shares that had been issued and were previously outstanding but which are now held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares used to settle grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of new stock issued during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=27012166&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number, after forfeiture, of shares or units issued under share-based payment arrangement. Excludes shares or units issued under employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=27012166&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=6877327&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=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodValueNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Equity impact of the value of new stock issued during the period. Includes shares issued in an initial public offering or a secondary public offering.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=27012166&amp;loc=d3e187085-122770<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Value, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br><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 55<br> -Paragraph 4I<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4590271-111686<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 15<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568447-111683<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_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>42
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6623887856">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 and nine months ended&#160;September 30, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 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 " 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. </span>In July 2017, Akcea completed an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO,</span> and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx.</sub>. At September 30, 2019, our ownership was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx</sub>. We reflect changes in our ownership of Akcea in our financial statements in the period the change occurs. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled &#8220;Noncontrolling Interest in Akcea&#8221; in Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies,</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further information related to our accounting for our investment in Akcea.</span></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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.3A-02)<br> -URI http://asc.fasb.org/extlink&amp;oid=116822174&amp;loc=d3e355033-122828<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 S99<br> -Paragraph 3<br> -Subparagraph (SX 210.3A-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=116822174&amp;loc=d3e355100-122828<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=84158767&amp;loc=d3e18780-107790<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>43
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6636831552">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Operating Leases<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LeasesAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeasesTextBlock', window );">Operating Leases</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Operating Leases</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to two&#160;five-year periods.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease additional office space and we sublease a portion of this space to Akcea. We lease this space under a non-cancelable operating lease with an initial term ending in June 2023 and an option to extend the lease for one&#160;five-year period. The sublease with Akcea is eliminated in our condensed consolidated financial statements.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea entered into an operating lease agreement for office space located in Boston, Massachusetts for its new corporate headquarters in the second quarter of 2018. The lease commencement date was in August 2018 and Akcea took occupancy in September 2018. Akcea is leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an additional five-year term. Under the lease agreement, Akcea received a three-month free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. Akcea provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of the rent commencement date if Akcea meets certain conditions set forth in the lease at each such time.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include the extension options for these leases.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>

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

<table cellpadding="0" cellspacing="0" id="zf42106fcdfa447c3a605f18b4bb6c5cc" 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: center;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">At September 30, 2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom">&#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: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z134ddf538270485d8e34269956271e23" 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 deposits and other assets on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb6759401030e41a8ab46de882c820315" 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;">Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the nine months ended&#160;September 30, 2019, we paid $2.9 million of rent payments, which was included in operating activities in our condensed consolidated statement of cash flows.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2019, the payments for our operating lease liabilities are as follows (in thousands):</div>

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

<table cellpadding="0" cellspacing="0" id="zb029d562d7d14830957cb4fe63551490" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Remainder of 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">801</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Years ending December 31,</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,282</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2022</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,781</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,520</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,264</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imputed interest</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,533</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating lease liabilities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,731</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $0.8 million and $1.0 million for the three months ended September 30, 2019 and 2018, respectively. Rent expense was $2.7 million and $1.8 million for the nine months ended&#160;September 30, 2019 and 2018, respectively.</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_LeasesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_LeasesAbstract</td>
</tr>
<tr>
<td style="padding-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_LesseeOperatingLeasesTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 operating leases of lessee. Includes, but is not limited to, description of operating lease and maturity analysis of operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -URI http://asc.fasb.org/subtopic&amp;trid=77888251<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeasesTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>44
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6827636352">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsCurrentAbstract', window );"><strong>Current assets:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents</a></td>
<td class="nump">$ 247,939<span></span>
</td>
<td class="nump">$ 278,820<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Short-term investments</a></td>
<td class="nump">1,972,891<span></span>
</td>
<td class="nump">1,805,252<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">49,077<span></span>
</td>
<td class="nump">12,759<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">19,375<span></span>
</td>
<td class="nump">8,582<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">118,809<span></span>
</td>
<td class="nump">102,473<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,408,091<span></span>
</td>
<td class="nump">2,207,886<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">148,717<span></span>
</td>
<td class="nump">132,160<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FiniteLivedIntangibleAssetsNet', window );">Patents, net</a></td>
<td class="nump">26,985<span></span>
</td>
<td class="nump">24,032<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent', window );">Long-term deferred tax assets</a></td>
<td class="nump">284,997<span></span>
</td>
<td class="nump">290,796<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">26,199<span></span>
</td>
<td class="nump">12,910<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,894,989<span></span>
</td>
<td class="nump">2,667,784<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">13,146<span></span>
</td>
<td class="nump">28,660<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">24,404<span></span>
</td>
<td class="nump">29,268<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">52,615<span></span>
</td>
<td class="nump">47,503<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">1,945<span></span>
</td>
<td class="nump">858<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">2,060<span></span>
</td>
<td class="nump">13,749<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">137,607<span></span>
</td>
<td class="nump">160,256<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">231,777<span></span>
</td>
<td class="nump">280,294<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">492,979<span></span>
</td>
<td class="nump">567,359<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">1 percent convertible senior notes</a></td>
<td class="nump">596,355<span></span>
</td>
<td class="nump">568,215<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LongTermObligationsNoncurrent', window );">Long-term obligations, less current portion</a></td>
<td class="nump">16,016<span></span>
</td>
<td class="nump">4,914<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermLoansFromBank', window );">Long-term mortgage debt</a></td>
<td class="nump">59,896<span></span>
</td>
<td class="nump">59,842<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,397,023<span></span>
</td>
<td class="nump">1,480,624<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockValue', window );">Common stock, $0.001 par value; 300,000,000 shares authorized, 140,636,397 and 137,928,828 shares issued and outstanding at September 30, 2019 (unaudited) and December 31, 2018, respectively</a></td>
<td class="nump">141<span></span>
</td>
<td class="nump">138<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,219,090<span></span>
</td>
<td class="nump">2,047,250<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(25,375)<span></span>
</td>
<td class="num">(32,016)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(857,563)<span></span>
</td>
<td class="num">(967,293)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Total Ionis stockholders' equity</a></td>
<td class="nump">1,336,293<span></span>
</td>
<td class="nump">1,048,079<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_MinorityInterest', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">161,673<span></span>
</td>
<td class="nump">139,081<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Total stockholders' equity</a></td>
<td class="nump">1,497,966<span></span>
</td>
<td class="nump">1,187,160<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">$ 2,894,989<span></span>
</td>
<td class="nump">$ 2,667,784<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccountsPayableCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccountsPayableCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedIncomeTaxesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying amount as of the balance sheet date of the unpaid sum of the known and estimated amounts payable to satisfy all currently due domestic and foreign income tax obligations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(b)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=119400593&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=6876686&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=6877327&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=6877327&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://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=118930883&amp;loc=d3e637-108580<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 14A<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669686-108580<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 14<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&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=6877327&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=6876686&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 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<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)(12))<br> -URI http://asc.fasb.org/extlink&amp;oid=119400593&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_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=118951113&amp;loc=d3e6801-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118951113&amp;loc=d3e6676-107765<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118942338&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=118954083&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=118932676&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=118951113&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=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashAndCashEquivalentsAtCarryingValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Aggregate par or stated value of issued nonredeemable common stock (or common stock redeemable solely at the option of the issuer). This item includes treasury stock repurchased by the entity. Note: elements for number of nonredeemable common shares, par value and other disclosure concepts are in another section within stockholders' equity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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=118944033&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=118944033&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=118956577&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=118944033&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=118944033&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=118956577&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=118944033&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=118944033&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=118956577&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=6877327&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_DeferredTaxAssetsLiabilitiesNetNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after allocation of valuation allowances and deferred tax liability, of deferred tax asset attributable to deductible differences and carryforwards, with jurisdictional netting and classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=116821951&amp;loc=d3e31917-109318<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=84230637&amp;loc=d3e32537-109319<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=116821951&amp;loc=d3e31931-109318<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsLiabilitiesNetNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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=6877327&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://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=118951113&amp;loc=d3e6676-107765<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=116846819&amp;loc=d3e3927-108312<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=6877327&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=6877327&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_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://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=6876686&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=119400593&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(32))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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_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://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=6877327&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_LongTermDebtAndCapitalLeaseObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt and lease obligation, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtAndCapitalLeaseObligationsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=6877327&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=6876686&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=119400593&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermLoansFromBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which is directly or indirectly attributable to that ownership interest in subsidiary equity which is not attributable to the parent (that is, noncontrolling interest, previously referred to as minority interest).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(24))<br> -URI http://asc.fasb.org/extlink&amp;oid=119400593&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.31)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=6876686&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_MinorityInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of current assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of noncurrent assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.17)<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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=6877327&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=119400593&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RetainedEarningsAccumulatedDeficit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The cumulative amount of the reporting entity's undistributed earnings or deficit.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=119400593&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 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=27012166&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -URI http://asc.fasb.org/extlink&amp;oid=27010918&amp;loc=d3e74512-122707<br><br>Reference 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(31))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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(30))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&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_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_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568740-111683<br><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 55<br> -Paragraph 4I<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4590271-111686<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 15<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4568447-111683<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_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>45
<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>46
<FILENAME>R43.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6827306800">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>USD ($) </div>
<div>Target </div>
<div>Payment</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SPINRAZARoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">81,672<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,010<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">211,884<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 72,193<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">62,639<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 376,833<span></span>
</td>
<td class="nump">225,584<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations', window );">Number of medicines currently in development under collaborations | Medicine</a></td>
<td class="nump">8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 2,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">107,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 104,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">293,800<span></span>
</td>
<td class="nump">$ 234,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 532,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 532,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 580,900<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">64.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">72.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">47.00%<span></span>
</td>
<td class="nump">58.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 81,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 211,900<span></span>
</td>
<td class="nump">$ 167,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">25,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 34,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">81,900<span></span>
</td>
<td class="nump">$ 66,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">2018 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_UpfrontPaymentReceivedIncludingPurchaseOfStock', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_NumberOfMilestonePaymentsAchieved', window );">Number of milestone payments achieved | Payment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MilestonePaymentsReceived', window );">Milestone payment received</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="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_NumberOfNewTargetsAdvanced', window );">Number of new targets advanced | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="nump">7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember', window );">2018 Strategic Neurology [Member] | R&amp;D Services [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="nump">582,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">582,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="num">(16,500)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="nump">145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | IONIS-LRRK2 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">8,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">2012 Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">6,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MilestonePaymentsReceived', window );">Milestone payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="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="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_NextPotentialMilestonePayment', window );">Next prospective milestone</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="nump">10,000<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">2012 Neurology [Member] | R&amp;D Services [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="nump">40,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">40,000<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember', window );">2012 Neurology [Member] | IONIS-MAPT [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Payments included in transaction price for performance obligation</a></td>
<td class="nump">$ 25,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,500<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_MilestonePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of milestone payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MilestonePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 milestone 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_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of medicines currently in development under collaborations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations</td>
</tr>
<tr>
<td style="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_NumberOfMilestonePaymentsAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 milestone payments achieved 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_NumberOfMilestonePaymentsAchieved</td>
</tr>
<tr>
<td style="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_NumberOfNewTargetsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of new targets advanced 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_NumberOfNewTargetsAdvanced</td>
</tr>
<tr>
<td style="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_PaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_UpfrontPaymentReceivedIncludingPurchaseOfStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceivedIncludingPurchaseOfStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://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 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=118260190&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 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118260190&amp;loc=d3e13537-108611<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 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118944033&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=118956577&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=118944033&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 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SPINRAZARoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SPINRAZARoyaltiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentServicesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_IONISLRRK2Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_IONISLRRK2Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></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_IONISMAPTMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_IONISMAPTMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>47
<FILENAME>R47.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6808200176">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Novartis (Details) - USD ($)<br> $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Mar. 31, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">72,193<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 62,639<span></span>
</td>
<td class="nump">376,833<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 10,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 28,800<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">5.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5.00%<span></span>
</td>
<td class="nump">28.00%<span></span>
</td>
<td class="nump">10.00%<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 343,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 343,000<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | AKCEA-APO(a)-L [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " 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">5,500<span></span>
</td>
<td class="nump">$ 150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 8,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,200<span></span>
</td>
<td class="nump">$ 176,300<span></span>
</td>
<td class="nump">$ 42,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_SublicenseFeePaidForLicenseOfDrug', window );">Sublicense fee paid in stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ReceiptOfSharesInSubsidiary', window );">Additional shares of Akcea stock received (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_ReceiptOfSharesInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 received from the subsidiary during the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ReceiptOfSharesInSubsidiary</td>
</tr>
<tr>
<td style="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_SublicenseFeePaidForLicenseOfDrug">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of the sublicense fee paid in common stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_SublicenseFeePaidForLicenseOfDrug</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_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://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 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=118260190&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 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118260190&amp;loc=d3e13537-108611<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 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118944033&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=118956577&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=118944033&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 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_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_ProductOrServiceAxis=ions_AKCEAAPOALMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.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_AKCEAAPOALMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>48
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6627817648">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Contracts Receivable (Details)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PeriodAfterBillingWhenPaymentIsReceived', window );">Period of time after billing when payment is received</a></td>
<td class="text">3 months<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<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_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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>49
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6811392016">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z20353bec45cf4f6e84901f27ae49c055" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">107.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">104.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">234.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27.1pt; 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%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z2a013d4519bd47b387164e642d8d6b5c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z5a49728eb04942b281219a3239b033e8" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="zd0e86e09a7c74df9a1e6577ab1ae4307" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems</td>
</tr>
<tr>
<td style="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=118260190&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=118260190&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsBiogenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>50
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6978336192">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock', window );">Basic Net Income (Loss) per Share</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,221</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.34</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,772</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,772</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,930</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,551</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.40</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,174</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,174</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,938</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,538</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.73</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47,843</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47,843</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,346</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.03</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.93</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,680</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,680</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,517</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43,163</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.33</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock', window );">Basic and Diluted Net Income Per Share</a></td>
<td class="text"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the three months ended September 30, 2019</span></span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"> as follows (in thousands except per share amounts):</span></span>
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,551</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,993</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">844</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,408</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the nine months ended&#160;September 30, 2019 as follows (in thousands except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,208</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">793</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">142,821</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.79</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr 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_ShareBasedCompensationLineItems', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text">
<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#160;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

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

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

<table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.1</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; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text">
<table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">45.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock', window );">Stock-Based Compensation Expense</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands).</div>

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

<table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/>
    <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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">Cost of products sold</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,744</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,780</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,935</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,698</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">255</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,103</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,246</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total non-cash stock-based compensation expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,126</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,883</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111,564</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97,210</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationLineItems', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">&#160;</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">September 30, 2019</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"> and 2018</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">: </span>
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

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

<table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.7</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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">75.6</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;">77.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">1.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">73.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.4 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;">Akcea ESPP:</span>
<table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; 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_ShareBasedCompensationLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_ShareBasedCompensationLineItems</td>
</tr>
<tr>
<td style="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_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_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 an entity's basic and diluted earnings per share calculations, including a reconciliation of numerators and denominators of the basic and diluted per-share computations for income from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 effect of income (loss) on basic earnings per share.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=117327953&amp;loc=d3e4984-109258<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 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1252-109256<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1278-109256<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_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=116856206&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=115993241&amp;loc=d3e301413-122809<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=116856206&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=116856206&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=116856206&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>51
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6668423200">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#160;September 30, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. </span>In July 2017, Akcea completed an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO,</span> and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx.</sub>. At September 30, 2019, our ownership was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx</sub>. We reflect changes in our ownership of Akcea in our financial statements in the period the change occurs. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to the section titled &#8220;Noncontrolling Interest in Akcea&#8221; in Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies,</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further information related to our accounting for our investment in Akcea.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unless the context requires otherwise, &#8220;Ionis&#8221;, &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and its majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries.</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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>52
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6824302832">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited) - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpensesAbstract', window );"><strong>Expenses:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of products sold</a></td>
<td class="nump">967<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,373<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">104,366<span></span>
</td>
<td class="nump">95,255<span></span>
</td>
<td class="nump">316,948<span></span>
</td>
<td class="nump">301,153<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">60,036<span></span>
</td>
<td class="nump">68,712<span></span>
</td>
<td class="nump">203,368<span></span>
</td>
<td class="nump">178,563<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">165,369<span></span>
</td>
<td class="nump">163,967<span></span>
</td>
<td class="nump">523,689<span></span>
</td>
<td class="nump">479,716<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Income (loss) from operations</a></td>
<td class="nump">2,523<span></span>
</td>
<td class="num">(18,572)<span></span>
</td>
<td class="nump">105,229<span></span>
</td>
<td class="num">(72,157)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NonoperatingIncomeExpenseAbstract', window );"><strong>Other income (expense):</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentIncomeNet', window );">Investment income</a></td>
<td class="nump">13,136<span></span>
</td>
<td class="nump">9,963<span></span>
</td>
<td class="nump">39,015<span></span>
</td>
<td class="nump">18,711<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(12,002)<span></span>
</td>
<td class="num">(11,282)<span></span>
</td>
<td class="num">(35,404)<span></span>
</td>
<td class="num">(33,332)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other income (expenses)</a></td>
<td class="num">(140)<span></span>
</td>
<td class="num">(22)<span></span>
</td>
<td class="num">(332)<span></span>
</td>
<td class="num">(145)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments', window );">Income (loss) before income tax (expense) benefit</a></td>
<td class="nump">3,517<span></span>
</td>
<td class="num">(19,913)<span></span>
</td>
<td class="nump">108,508<span></span>
</td>
<td class="num">(86,923)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax (expense) benefit</a></td>
<td class="nump">14,915<span></span>
</td>
<td class="num">(452)<span></span>
</td>
<td class="num">(9,204)<span></span>
</td>
<td class="num">(824)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="nump">18,432<span></span>
</td>
<td class="num">(20,365)<span></span>
</td>
<td class="nump">99,304<span></span>
</td>
<td class="num">(87,747)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest', window );">Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">7,732<span></span>
</td>
<td class="nump">15,806<span></span>
</td>
<td class="nump">10,426<span></span>
</td>
<td class="nump">41,412<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">$ 26,163<span></span>
</td>
<td class="num">$ (4,559)<span></span>
</td>
<td class="nump">$ 109,730<span></span>
</td>
<td class="num">$ (46,335)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.19<span></span>
</td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="nump">$ 0.81<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net income (loss) per share (in shares)</a></td>
<td class="nump">140,551<span></span>
</td>
<td class="nump">137,346<span></span>
</td>
<td class="nump">139,800<span></span>
</td>
<td class="nump">130,507<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.18<span></span>
</td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="nump">$ 0.79<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income (loss) per share (in shares)</a></td>
<td class="nump">143,408<span></span>
</td>
<td class="nump">137,346<span></span>
</td>
<td class="nump">142,821<span></span>
</td>
<td class="nump">130,507<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_srt_ProductOrServiceAxis=ions_CommercialMember', window );">Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 95,699<span></span>
</td>
<td class="nump">$ 82,756<span></span>
</td>
<td class="nump">$ 252,085<span></span>
</td>
<td class="nump">$ 181,975<span></span>
</td>
</tr>
<tr 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_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">81,672<span></span>
</td>
<td class="nump">70,010<span></span>
</td>
<td class="nump">211,884<span></span>
</td>
<td class="nump">167,743<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">Product Sales, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">11,945<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">28,563<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">2,082<span></span>
</td>
<td class="nump">12,746<span></span>
</td>
<td class="nump">11,638<span></span>
</td>
<td class="nump">14,232<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">Research and Development Revenue Under Collaborative Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 72,193<span></span>
</td>
<td class="nump">$ 62,639<span></span>
</td>
<td class="nump">$ 376,833<span></span>
</td>
<td class="nump">$ 225,584<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://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=116634182&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=116634182&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 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637232&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 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1337-109256<br><br>Reference 3: 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=117327953&amp;loc=d3e4984-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<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> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<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 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1252-109256<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637391&amp;loc=SL114874048-224260<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=SL5780133-109256<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_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI http://asc.fasb.org/extlink&amp;oid=117327953&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 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1252-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><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(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637391&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 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1337-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<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=117326831&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 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637232&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_EarningsPerShareDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations before deduction of income tax expense (benefit) and income (loss) attributable to noncontrolling interest, and addition of income (loss) from equity method investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08.(h)(1)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=26873400&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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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=26873400&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109238882&amp;loc=d3e38679-109324<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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=114775744&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=115929826&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=116634182&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=116637391&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 210.5-03.9)<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&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 210.5-03.7(a),(b))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&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 S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentIncomeNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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=116637391&amp;loc=SL114874048-224260<br><br>Reference 3: 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=118930883&amp;loc=SL7669625-108580<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=116637232&amp;loc=SL114874131-224263<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 S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<br><br>Reference 6: 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=118932676&amp;loc=d3e3602-108585<br><br>Reference 7: 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> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of Net Income (Loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591551-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NonoperatingIncomeExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NonoperatingIncomeExpenseAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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=116634182&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherNonoperatingIncomeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<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=115929826&amp;loc=d3e8736-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591551-111686<br><br>Reference 7: 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 2<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&amp;loc=d3e3000-108585<br><br>Reference 8: 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 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591552-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_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 330<br> -SubTopic 10<br> -Section 30<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=68048583&amp;loc=d3e3636-108311<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 210.5-03.4)<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&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://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 (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&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://fasb.org/us-gaap/role/ref/legacyRef<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=117326831&amp;loc=d3e1448-109256<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 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>53
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6665182288">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_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 " 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;">7.&#160; Collaborative Arrangements and Licensing Agreements</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our collaborations with substantive changes during the first nine months of 2019 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2018.</span></div>

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

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

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

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

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

<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 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. In</span> December 2017, we entered into a collaboration with Biogen to identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and Biogen are currently developing </span>eight<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> medicines under collaborations, including medicines to treat people with ALS, Alzheimer&#8217;s disease</span><sub>&#160;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 September 2019, we have received $</span>2.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion from our Biogen collaborations, including $</span>1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion we received from Biogen in the second quarter of 2018 for our 2018 strategic neurology collaboration.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z20353bec45cf4f6e84901f27ae49c055" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">107.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">104.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">234.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27.1pt; 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%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</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; font-weight: bold;">Neurology Collaborations</div>

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

<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;">2018 Strategic Neurology</div>

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

<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 second quarter of 2019, we achieved two $7.5 million milestone payments from Biogen when we advanced two new targets for unidentified neurological diseases<sub>&#160;</sub>under this collaboration. These milestone payments did not create new performance obligations because they are part of our original R&amp;D services performance obligation. Therefore, we included these amounts in our transaction price for our R&amp;D services performance obligation. We are recognizing revenue for our R&amp;D services performance obligation based on the percentage of completion. From inception through September 2019, we have included $582 million in payments in the transaction price for our R&amp;D services performance obligation under this collaboration. We currently estimate we will satisfy our performance obligation in June 2028.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will achieve the next payment of $7.5 million if Biogen designates another target under this collaboration.</div>

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

<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;">2013 Strategic Neurology</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2019, we achieved an $8 million milestone payment when Biogen initiated a Phase 1/2 study of ION859 (IONIS-LRRK2<sub>Rx</sub>) <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the treatment of people with Parkinson&#8217;s disease </span>under this collaboration. We concluded that this milestone payment was not related to our R&amp;D services performance obligation. Therefore, we recognized the $8 million milestone payment in full in the third quarter of 2019 because we do not have any performance obligations related to this payment.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through September 2019, we have included $145 million in total payments in the transaction price for our R&amp;D services performance obligation under this collaboration that we are recognizing over our estimated period of performance. We are recognizing revenue as we perform services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. In the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation. As of September 30, 2019, we have completed a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> significant portion of the research and development services. We expect to complete the remainder of our services in 2020. </span>As a result, we recorded a cumulative catch up adjustment of $16.5 million to decrease revenue in the third quarter of 2019. We will recognize this amount over the estimated remaining period we will perform services.</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced IONIS-MAPT<sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for Alzheimer&#8217;s disease</span> under this collaboration. This milestone payment did not create a new performance obligation because it is part of our performance obligation to conduct development of IONIS-MAPT<sub>Rx</sub>. Therefore, we included the $7.5 million milestone payment in our transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. We are recognizing revenue for our IONIS-MAPT<sub>Rx</sub> development performance obligation based on the percentage of completion. From inception through September 2019, we have included $25.5 million in the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation. We currently estimate we will satisfy our performance obligation in September 2020.</div>

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

<div 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 a separate performance obligation to perform R&amp;D services under this collaboration. We have allocated $40 million in total payments to the transaction price for our R&amp;D services performance obligation. In the third quarter of 2019, we completed our R&amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. Biogen&#8217;s decision to accept the development candidate was not within our control. We were recognizing revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. Because Biogen accepted the development candidate, we recognized $6.3 million of accelerated revenue in the third quarter of 2019.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will achieve the next payment of up to $10 million if we advance a program under this collaboration.</div>

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

<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 nine months of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Biogen collaborations, except as noted above.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2019 and December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred revenue of $532.4 million and $580.9 million, respectively, related to our relationship with Biogen.</div>

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

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

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize our programs targeting FXI for the treatment of clotting disorders. In October 2019, Bayer decided it would advance IONIS-FXI-L<sub>Rx</sub> following positive clinical results and we earned a $10 million milestone payment. At September 30, 2019, we determined that it was not probable that we could earn this milestone payment. As such, we did not recognize any revenue associated with it during the third quarter of 2019. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI program. From inception through September 2019, we have received over $175 million from our Bayer collaboration, not including the $10 million milestone payment we earned in the fourth quarter of 2019.&#160; We will achieve the next payment of $20 million when Bayer initiates a Phase 3 study under the FXI program.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK includes two drugs targeting hepatitis B virus, or HBV: IONIS-HBV<sub>Rx</sub> and IONIS-HBV-L<sub>Rx</sub>, which we designed to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program, for which we earned a $25 million license fee. From inception through September 2019, we have received more than $164 million in payments under our collaboration with GSK, not including the $25 million license fee, which we expect to receive in the fourth quarter of 2019. We will achieve the next payment of $15 million when GSK initiates a Phase 3 study for a drug under this program.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified a new performance obligation when we granted GSK the license of the HBV program and assignment of related intellectual property rights in the third quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $25 million license fee for the HBV program as revenue at that time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z2a013d4519bd47b387164e642d8d6b5c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any deferred revenue from our relationship with GSK at September 30, 2019 or December 31, 2018.</div>

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

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

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

<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 have </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> collaborations with Roche, </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to develop treatments for Huntington's disease, or HD, and </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. In December 2017, upon completion of the Phase 1/2 study of IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Roche exercised its option to license IONIS-HTT</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In October 2018, we entered into a collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases. The first indication we plan to pursue is the treatment of patients with geographic atrophy, or GA, the advanced stage of dry age-related macular degeneration, or AMD. We are responsible for conducting a Phase 2 study in patients with dry AMD. In addition, we plan to evaluate the medicine for a severe and rare renal indication. </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> has the option to license IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> at the completion of these studies. Upon licensing, </span>Roche <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for all further global development, regulatory and commercialization activities and costs.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through June 2019, we have received over $</span>220<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from our Roche collaborations, including $</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">milestone payments we earned in the first quarter of 2019 when Roche dosed the first patient in a Phase 3 study for IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We will achieve the next payment of $</span>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Roche advances IONIS-HTT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z5a49728eb04942b281219a3239b033e8" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our revenue in the first nine months of 2019 included $35 million of milestone payments we earned when Roche dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx</sub> in the first quarter of 2019. We recognized these milestone payments in full in the first quarter of 2019 because we do not have any performance obligations related to these milestone payments, as Roche is conducting the Phase 3 study of IONIS-HTT<sub>Rx</sub>.</div>

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

<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 nine months of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Roche collaborations.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at September 30, 2019 and December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred revenue of $56.7 million and $72.6 million, respectively, related to our relationship with Roche.</div>

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

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

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

<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 collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under this collaboration agreement. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and AKCEA-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span><sub>&#160;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and AKCEA-APOCIII-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the FDA and providing initial quantities of API for each medicine. If Novartis exercises an option for either of these medicines, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such medicine. </span>In the first quarter of 2019, Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>. Novartis is responsible for conducting and funding all future development, regulatory and commercialization activities for AKCEA-APO(a)-L<sub>Rx</sub>, including a global pivotal cardiovascular outcomes study, for which planning and initiation activities are underway. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through September 2019, we have received over $</span>343<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from our Novartis collaboration, including $</span>150<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we earned from Novartis in the first quarter of 2019 for the license of AKCEA-APO(a)-L</span><sub>Rx</sub>. Akcea paid us $75 million as a sublicense fee in 2.8 million shares of Akcea common stock.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We identified a new performance obligation when we granted Novartis the license of AKCEA-APO(a)-L<sub>Rx</sub> in the first quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $150 million license fee for AKCEA-APO(a)-L<sub>Rx</sub> as revenue at that time because Novartis had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Novartis.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis has the option to purchase additional API of AKCEA-APO(a)-L<sub>Rx</sub> in the future at agreed upon terms and conditions under our collaboration agreement. We identified a new performance obligation when we delivered additional AKCEA-APO(a)-L<sub>Rx</sub> API to Novartis in the third quarter of 2019 because the delivery of the API is distinct from our other performance obligations. We recognized $5.5&#160; million in revenue for the API we sold to Novartis in the third quarter of 2019.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea is responsible for the development activities under this collaboration. As such, Akcea is recognizing the associated revenue in its statement of operations, and we reflect all of Akcea&#8217;s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core operating segment results and Akcea recognizes the fees as R&amp;D expense. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our condensed consolidated balance sheet.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="zd0e86e09a7c74df9a1e6577ab1ae4307" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the first nine months of 2019, we did not have any changes to our performance obligations, except as noted above, or the timing in which we expect to recognize revenue under our Novartis collaboration.</div>

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

<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 September 30, 2019 and December 31, 2018 included deferred revenue of $10.8 million and $28.8 million, respectively, related to our relationship with Novartis.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2019, Akcea initiated a collaboration with Pfizer for the license of AKCEA<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub> to treat people with cardiovascular and metabolic diseases. Akcea is currently conducting a Phase 2 study of AKCEA<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub> for the treatment of non-alcoholic fatty liver disease, or NAFLD. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the ongoing Phase 2 study.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, Akcea will receive a $</span>250<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront license fee, upon closing the transaction, including receiving Hart-Scott Rodino clearance. Akcea is also eligible to receive development, regulatory and sales milestone payments of up to $</span>1.3<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion and tiered royalties in the mid-teens to low-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on annual worldwide net sales. Akcea has retained the rights to co-commercialize AKCEA</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and certain additional markets. The license fee, milestone payments and royalties will be split equally between us and Akcea. Upon receipt of the upfront payment from Pfizer</span>, Akcea expects to pay us its $125 million sublicense fee in 6.9 million shares of Akcea common stock.</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In October 2019, Akcea initiated a collaboration with Pfizer for the license of AKCEA</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-ANGPTL3-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to treat people with cardiovascular and metabolic diseases. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, Akcea will receive a $</span>250<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront license fee, upon closing the transaction, including receiving Hart-Scott Rodino clearance. </span>Akcea is also eligible to receive development, regulatory and sales milestone payments of up to $1.3 billion and tiered royalties<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the mid-teens to low-20 percent range </span>on annual worldwide net sales. Akcea will pay us 50 percent of the license fee, milestone payments and royalties. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the ongoing Phase 2 study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Upon receipt of the upfront payment from Pfizer</span>, Akcea expects to pay us its $125 million sublicense fee in 6.9 million shares of Akcea common stock.</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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>54
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6636831552">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_invest_InvestmentTextBlock', window );">Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 0.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2019, we had invested our excess cash primarily in debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>

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

<div style="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 September 30, 2019:</div>

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

<table cellpadding="0" cellspacing="0" id="zcf07523367524c41877d56d489917e98" 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;">One year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After one year but within two years</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After two years but within three years</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: 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; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at September 30, 2019, 91 percent of our available-for-sale securities had a maturity of less than two years.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 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;">At September 30, 2019, we had an ownership interest of less than 20 percent in four private companies and two public companies with which we conduct business. The privately-held companies are Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly-traded companies are ProQR and ATL.</div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following is a summary of our investments (in thousands):</span></div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" id="zb56166283a7847d5befc091adecaa6a1" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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; font-weight: bold;">September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">752,495</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,484</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(148</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">753,831</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,589</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(45</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,865</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331,371</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">264</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331,618</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,986</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,963</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,297,389</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,073</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(237</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,299,225</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">539,820</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,108</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,767</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106,536</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(137</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106,500</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">34,692</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">(38</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,654</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,283</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,302</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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;">690,331</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,234</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(342</div></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;">693,223</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,987,720</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,307</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(579</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,992,448</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,988,932</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5,307</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,185</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,993,054</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="zf8befa7024ac4c7aaab0e6b0e3be21d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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; font-weight: bold;">December 31, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">956,879</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,858</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">955,034</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">168,839</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(104</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">168,738</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">244,640</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(77</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">244,578</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63,572</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(323</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63,249</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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;">1,433,930</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,362</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,431,599</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">299,018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">194</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,286</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">297,926</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">107,789</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">194</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(109</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">107,874</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,600</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,576</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,980</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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;">(287</div></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;">16,693</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">439,387</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">388</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,706</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438,069</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,873,317</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,068</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,869,668</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current 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;">1,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,874,529</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">556</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,068</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,871,017</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze2689b040009421da56fad38f1ad9a5f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our available-for-sale securities are held at amortized cost.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4c2e520a6c644d0f8f16eee8ae381f87" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z94b340357ef0469db6ab0f6c9e7f6ab9" 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;">We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2019. 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.</div>

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

<table cellpadding="0" cellspacing="0" id="z78a191fc6a1c47b5bbf4c2cc8e099df3" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;(In thousands)</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">104</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">304,705</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(268</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,675</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(41</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">336,380</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(309</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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%; background-color: #FFFFFF; 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%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">102,733</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(156</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,974</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(26</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">125,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,918</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">(55</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#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;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,918</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">(55</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #FFFFFF; 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%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,498</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,597</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,095</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(33</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">486,854</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(480</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,246</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(99</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">557,100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(579</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_invest_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 investments, including all tables.</p></div>
<a 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-X (SX)<br> -Number 210<br> -Article 6<br> -Section 10<br> -Paragraph (c)<br> -Subparagraph (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;">invest_InvestmentTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>invest_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>55
<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/2019-01-31"
  xmlns:invest="http://xbrl.sec.gov/invest/2013-01-31"
  xmlns:ions="http://isispharm.com/20190930"
  xmlns:iso4217="http://www.xbrl.org/2003/iso4217"
  xmlns:link="http://www.xbrl.org/2003/linkbase"
  xmlns:srt="http://fasb.org/srt/2019-01-31"
  xmlns:us-gaap="http://fasb.org/us-gaap/2019-01-31"
  xmlns:xbrldi="http://xbrl.org/2006/xbrldi"
  xmlns:xlink="http://www.w3.org/1999/xlink">
    <link:schemaRef xlink:href="ions-20190930.xsd" xlink:type="simple"/>
    <context id="c20190101to20190930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20191031">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2019-10-31</instant>
        </period>
    </context>
    <context id="c20181231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190630_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-06-30</instant>
        </period>
    </context>
    <context id="c20190630_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>2019-06-30</instant>
        </period>
    </context>
    <context id="c20171231_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>2017-12-31</instant>
        </period>
    </context>
    <context id="c20181231_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20171231_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2017-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20171231_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2017-12-31</instant>
        </period>
    </context>
    <context id="c20180630_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>2018-06-30</instant>
        </period>
    </context>
    <context id="c20190630_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-06-30</instant>
        </period>
    </context>
    <context id="c20171231_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>2017-12-31</instant>
        </period>
    </context>
    <context id="c20171231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2017-12-31</instant>
        </period>
    </context>
    <context id="c20181231_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20171231_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>2017-12-31</instant>
        </period>
    </context>
    <context id="c20190630_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>2019-06-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20180630_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>2018-06-30</instant>
        </period>
    </context>
    <context id="c20180630_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>2018-06-30</instant>
        </period>
    </context>
    <context id="c20190630_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>2019-06-30</instant>
        </period>
    </context>
    <context id="c20180630">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2018-06-30</instant>
        </period>
    </context>
    <context id="c20171231_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>2017-12-31</instant>
        </period>
    </context>
    <context id="c20180630_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>2018-06-30</instant>
        </period>
    </context>
    <context id="c20190630">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2019-06-30</instant>
        </period>
    </context>
    <context id="c20180630_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-06-30</instant>
        </period>
    </context>
    <context id="c20180630_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-06-30</instant>
        </period>
    </context>
    <context id="c20190630_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>2019-06-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180930_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>2018-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:NoncontrollingInterestMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-09-30</instant>
        </period>
    </context>
    <context id="c20180930_StatementEquityComponentsAxis_ParentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:ParentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-09-30</instant>
        </period>
    </context>
    <context id="c20180930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2018-09-30</instant>
        </period>
    </context>
    <context id="c20180930_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>2018-09-30</instant>
        </period>
    </context>
    <context id="c20180930_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>2018-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20180930_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>2018-09-30</instant>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2017-06-30</instant>
        </period>
    </context>
    <context id="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-03-31</endDate>
        </period>
    </context>
    <context id="c20191001to20191231_OwnershipAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:StatementScenarioAxis">srt:ScenarioForecastMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-10-01</startDate>
            <endDate>2019-12-31</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-03-31</endDate>
        </period>
    </context>
    <context id="c20190401to20190630_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-04-01</startDate>
            <endDate>2019-06-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:IONISLRRK2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2017-02-01</startDate>
            <endDate>2017-02-28</endDate>
        </period>
    </context>
    <context id="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2015-05-01</startDate>
            <endDate>2015-05-31</endDate>
        </period>
    </context>
    <context id="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-10-01</startDate>
            <endDate>2018-12-31</endDate>
        </period>
    </context>
    <context id="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-04-01</startDate>
            <endDate>2019-06-30</endDate>
        </period>
    </context>
    <context id="c20170228_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBayerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2017-02-28</instant>
        </period>
    </context>
    <context id="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2017-02-28</instant>
        </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="c20170731_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2017-07-31</instant>
        </period>
    </context>
    <context id="c20181231_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20180430_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-04-30</instant>
        </period>
    </context>
    <context id="c20190331_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-03-31</instant>
        </period>
    </context>
    <context id="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AdjustmentsForNewAccountingPronouncementsAxis">us-gaap:AccountingStandardsUpdate201602Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementClassOfStockAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:OwnershipAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_RestrictedStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_AwardTypeAxis_RestrictedStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180930_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>2018-09-30</instant>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:BoardOfDirectorStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_EmployeeMember">
        <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:RelatedPartyTransactionsByRelatedPartyAxis">ions:EmployeeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_BoardOfDirectorsMember">
        <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:RelatedPartyTransactionsByRelatedPartyAxis">ions:BoardOfDirectorsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190531_PlanNameAxis_EquityIncentivePlan2011Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PlanNameAxis">ions:EquityIncentivePlan2011Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-05-31</instant>
        </period>
    </context>
    <context id="c20190630_PlanNameAxis_EquityIncentivePlan2011Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PlanNameAxis">ions:EquityIncentivePlan2011Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-06-30</instant>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_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>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_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>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_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>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_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>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190901to20190930">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2019-09-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentTypeAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentTypeAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20180101to20181231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-12-31</endDate>
        </period>
    </context>
    <context id="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentTypeAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_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>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_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>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceSubleasedToAkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceSubleasedToAkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceForCorporateHeadquartersMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">ions:OfficeSpaceForCorporateHeadquartersMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-04-01</startDate>
            <endDate>2018-06-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-04-01</startDate>
            <endDate>2019-06-30</endDate>
        </period>
    </context>
    <context id="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentServicesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_ProductOrServiceAxis_IONISMAPTMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:IONISMAPTMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentServicesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsBiogenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20191001to20191031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:SubsequentEventTypeAxis">us-gaap:SubsequentEventMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-10-01</startDate>
            <endDate>2019-10-31</endDate>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <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:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:LicenseMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <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:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementsAndLicensingAgreementsRocheMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <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:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-03-31</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:AKCEAAPOALMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190331_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:AKCEAAPOALMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-03-31</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <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:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:SubsequentEventTypeAxis">us-gaap:SubsequentEventMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-10-31</instant>
        </period>
    </context>
    <context id="c20191001to20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:SubsequentEventTypeAxis">us-gaap:SubsequentEventMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-10-01</startDate>
            <endDate>2019-10-31</endDate>
        </period>
    </context>
    <context id="c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidatedEntitiesAxis">ions:AkceaTherapeuticsIncMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:StatementScenarioAxis">srt:ScenarioForecastMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-10-01</startDate>
            <endDate>2019-12-31</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-01-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-07-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-01-01</startDate>
            <endDate>2018-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SPINRAZARoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2019-07-01</startDate>
            <endDate>2019-09-30</endDate>
        </period>
    </context>
    <context id="c20190930_ConsolidationItemsAxis_IntersegmentEliminationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </period>
    </context>
    <context id="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_ConsolidationItemsAxis_IntersegmentEliminationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:IntersegmentEliminationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:AkceaTherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2018-12-31</instant>
        </period>
    </context>
    <context id="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ConsolidationItemsAxis">us-gaap:OperatingSegmentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:StatementBusinessSegmentsAxis">ions:IonisCoreMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2019-09-30</instant>
        </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:PerformanceObligation</measure>
    </unit>
    <unit id="U006">
        <measure>ions:Agreement</measure>
    </unit>
    <unit id="U007">
        <measure>ions:Company</measure>
    </unit>
    <unit id="U008">
        <measure>ions:Segment</measure>
    </unit>
    <unit id="U009">
        <measure>ions:Officer</measure>
    </unit>
    <unit id="U010">
        <measure>ions:Investment</measure>
    </unit>
    <unit id="U011">
        <measure>ions:Option</measure>
    </unit>
    <unit id="U012">
        <measure>ions:Medicine</measure>
    </unit>
    <unit id="U013">
        <measure>ions:Payment</measure>
    </unit>
    <unit id="U014">
        <measure>ions:Target</measure>
    </unit>
    <unit id="U015">
        <measure>ions:Drug</measure>
    </unit>
    <dei:EntityRegistrantName
      contextRef="c20190101to20190930"
      id="Fact_600dd95823ee443a90c01fa60e86a06d">IONIS PHARMACEUTICALS INC</dei:EntityRegistrantName>
    <dei:EntityCentralIndexKey
      contextRef="c20190101to20190930"
      id="Fact_df9e30b21d5640d7af3bead6ee6490b9">0000874015</dei:EntityCentralIndexKey>
    <dei:CurrentFiscalYearEndDate
      contextRef="c20190101to20190930"
      id="Fact_5134c462ce0049f1b2d4497db7061298">--12-31</dei:CurrentFiscalYearEndDate>
    <dei:AmendmentFlag
      contextRef="c20190101to20190930"
      id="Fact_f8436eb51608482a9a51314ed579886f">false</dei:AmendmentFlag>
    <dei:DocumentFiscalYearFocus
      contextRef="c20190101to20190930"
      id="Fact_ac6e42fd003745c7bb97630febb71ac5">2019</dei:DocumentFiscalYearFocus>
    <dei:DocumentFiscalPeriodFocus
      contextRef="c20190101to20190930"
      id="Fact_2790ecf0636d4ade949ac83e617495b0">Q3</dei:DocumentFiscalPeriodFocus>
    <ions:PeriodAfterBillingWhenPaymentIsReceived
      contextRef="c20190101to20190930"
      id="Fact_1b180806199c40a58d73092447ceea40">P3M</ions:PeriodAfterBillingWhenPaymentIsReceived>
    <dei:DocumentType
      contextRef="c20190101to20190930"
      id="Fact_9fcd2cdb7eb04c178e9dd2ab1d03f020">10-Q</dei:DocumentType>
    <dei:DocumentQuarterlyReport
      contextRef="c20190101to20190930"
      id="Fact_4402cd610e3c4c7784fbd9a7ad693bc7">true</dei:DocumentQuarterlyReport>
    <dei:DocumentPeriodEndDate
      contextRef="c20190101to20190930"
      id="Fact_2b97f8d9ccd74e52bd2a1ad2ca28adbe">2019-09-30</dei:DocumentPeriodEndDate>
    <dei:DocumentTransitionReport
      contextRef="c20190101to20190930"
      id="Fact_dfb67515b57d446fbfa4cdfed68e05ec">false</dei:DocumentTransitionReport>
    <dei:EntityFileNumber
      contextRef="c20190101to20190930"
      id="Fact_3e579d3aafdc4090b092fe8d3c101f8e">000-19125</dei:EntityFileNumber>
    <dei:EntityIncorporationStateCountryCode
      contextRef="c20190101to20190930"
      id="Fact_293ac86583764385aa6d4d3384929ec4">DE</dei:EntityIncorporationStateCountryCode>
    <dei:EntityTaxIdentificationNumber
      contextRef="c20190101to20190930"
      id="Fact_5da20f5de6c54bc5aa8f25908e78486e">33-0336973</dei:EntityTaxIdentificationNumber>
    <dei:EntityAddressAddressLine1
      contextRef="c20190101to20190930"
      id="Fact_172771314c0d4f939bacbbddd3388314">2855 Gazelle Court</dei:EntityAddressAddressLine1>
    <dei:EntityAddressCityOrTown
      contextRef="c20190101to20190930"
      id="Fact_e9acebb9c7d2485495774f21d9f8edba">Carlsbad</dei:EntityAddressCityOrTown>
    <dei:EntityAddressStateOrProvince
      contextRef="c20190101to20190930"
      id="Fact_2920ce073ddc4ae18ab93dda07f49d47">CA</dei:EntityAddressStateOrProvince>
    <dei:EntityAddressPostalZipCode
      contextRef="c20190101to20190930"
      id="Fact_767de21bf7d24e0dbb420c77385846e3">92010</dei:EntityAddressPostalZipCode>
    <dei:CityAreaCode
      contextRef="c20190101to20190930"
      id="Fact_2dc9c533eea043b58d89bf1ec803479b">760</dei:CityAreaCode>
    <dei:LocalPhoneNumber
      contextRef="c20190101to20190930"
      id="Fact_9ffb5548083a43c28a9f8b7807388cbc">931-9200</dei:LocalPhoneNumber>
    <dei:Security12bTitle
      contextRef="c20190101to20190930"
      id="Fact_cef7ebd4a9374d22b9707aabeedac92f">Common Stock, $.001 Par Value</dei:Security12bTitle>
    <dei:SecurityExchangeName
      contextRef="c20190101to20190930"
      id="Fact_63e7e94cd180424c9970da0211c88bec">NASDAQ</dei:SecurityExchangeName>
    <dei:TradingSymbol
      contextRef="c20190101to20190930"
      id="Fact_e08c5f4a91b441a98bdeb1c688d2dc6a">IONS</dei:TradingSymbol>
    <dei:EntityCurrentReportingStatus
      contextRef="c20190101to20190930"
      id="Fact_eee89e18b8d947ef8eaa32cab0408571">Yes</dei:EntityCurrentReportingStatus>
    <dei:EntityInteractiveDataCurrent
      contextRef="c20190101to20190930"
      id="Fact_8390f7c177c04c5bbb8d0bd5eddf56e2">Yes</dei:EntityInteractiveDataCurrent>
    <dei:EntityFilerCategory
      contextRef="c20190101to20190930"
      id="Fact_31428acaf33441f0beadbf17b6c02814">Large Accelerated Filer</dei:EntityFilerCategory>
    <dei:EntitySmallBusiness
      contextRef="c20190101to20190930"
      id="Fact_ebbd406b283b4f998d5cefdb153525c0">false</dei:EntitySmallBusiness>
    <dei:EntityEmergingGrowthCompany
      contextRef="c20190101to20190930"
      id="Fact_5628b90d7c6644c2b1bff035392709df">false</dei:EntityEmergingGrowthCompany>
    <dei:EntityEmergingGrowthCompany
      contextRef="c20190101to20190930"
      id="Fact_e031ce3131bb4775b45521bee2ee7e85">false</dei:EntityEmergingGrowthCompany>
    <dei:EntityShellCompany
      contextRef="c20190101to20190930"
      id="Fact_491fd78eaea544c9ab3f3335b0fb5df4">false</dei:EntityShellCompany>
    <dei:EntityCommonStockSharesOutstanding
      contextRef="c20191031"
      decimals="INF"
      id="Fact_a0521e2fdc4644ee9ab0f0386210b487"
      unitRef="U001">140663254</dei:EntityCommonStockSharesOutstanding>
    <us-gaap:CashAndCashEquivalentsAtCarryingValue
      contextRef="c20190930"
      decimals="-3"
      id="Fact_58ab72fa50f24ffe98199f48fbe2c7f0"
      unitRef="U002">247939000</us-gaap:CashAndCashEquivalentsAtCarryingValue>
    <us-gaap:CashAndCashEquivalentsAtCarryingValue
      contextRef="c20181231"
      decimals="-3"
      id="Fact_a0cb8c640e1a44688ea7c7919293748f"
      unitRef="U002">278820000</us-gaap:CashAndCashEquivalentsAtCarryingValue>
    <us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_05d3c63942424d44b3a45d0e399d7509"
      unitRef="U002">1972891000</us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent>
    <us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_40b92a7d67634da98603b4b62a18fd2a"
      unitRef="U002">1805252000</us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent>
    <us-gaap:ContractWithCustomerAssetNetCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_42eb7b27d7ea459086945663ae763056"
      unitRef="U002">49077000</us-gaap:ContractWithCustomerAssetNetCurrent>
    <us-gaap:ContractWithCustomerAssetNetCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_90c87b1639e7454d862938e1695fb4ba"
      unitRef="U002">12759000</us-gaap:ContractWithCustomerAssetNetCurrent>
    <us-gaap:InventoryNet
      contextRef="c20190930"
      decimals="-3"
      id="Fact_bdc1851ec3a24426938e66ad4005713a"
      unitRef="U002">19375000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20181231"
      decimals="-3"
      id="Fact_efd195f3edec4c3091ff79a53462abb8"
      unitRef="U002">8582000</us-gaap:InventoryNet>
    <us-gaap:OtherAssetsCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_c0fa7bfa145e4eada7d79dd483724b5a"
      unitRef="U002">118809000</us-gaap:OtherAssetsCurrent>
    <us-gaap:OtherAssetsCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_a989f48740884b3f9c662b56d8ec6f22"
      unitRef="U002">102473000</us-gaap:OtherAssetsCurrent>
    <us-gaap:AssetsCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_4a277ae70920496a859de16b126a781a"
      unitRef="U002">2408091000</us-gaap:AssetsCurrent>
    <us-gaap:AssetsCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_e034b0a9b6284d72a53c220d22bd9ae4"
      unitRef="U002">2207886000</us-gaap:AssetsCurrent>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20190930"
      decimals="-3"
      id="Fact_4cf8028d82514177b93946aa1df7c264"
      unitRef="U002">148717000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20181231"
      decimals="-3"
      id="Fact_5ad23e93b4e4467b9feec47f0d291fee"
      unitRef="U002">132160000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:FiniteLivedIntangibleAssetsNet
      contextRef="c20190930"
      decimals="-3"
      id="Fact_edce7eb26c0445978fe4ae3f9eed3d07"
      unitRef="U002">26985000</us-gaap:FiniteLivedIntangibleAssetsNet>
    <us-gaap:FiniteLivedIntangibleAssetsNet
      contextRef="c20181231"
      decimals="-3"
      id="Fact_7f0d3ff8c03f42ccb4e063d20c964f58"
      unitRef="U002">24032000</us-gaap:FiniteLivedIntangibleAssetsNet>
    <us-gaap:DeferredTaxAssetsLiabilitiesNetNoncurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_27b7fc0a3c4943289d67893d78760afc"
      unitRef="U002">284997000</us-gaap:DeferredTaxAssetsLiabilitiesNetNoncurrent>
    <us-gaap:DeferredTaxAssetsLiabilitiesNetNoncurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_b78601c074a24e579332fef12795e70d"
      unitRef="U002">290796000</us-gaap:DeferredTaxAssetsLiabilitiesNetNoncurrent>
    <us-gaap:OtherAssetsNoncurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_d40d8e0c343c4faa8c8a1998eaa5093e"
      unitRef="U002">26199000</us-gaap:OtherAssetsNoncurrent>
    <us-gaap:OtherAssetsNoncurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_20e82d483df24cd682d948f6abcde7a0"
      unitRef="U002">12910000</us-gaap:OtherAssetsNoncurrent>
    <us-gaap:Assets
      contextRef="c20190930"
      decimals="-3"
      id="Fact_e57f61237ed14bad8578d2b47564ba8a"
      unitRef="U002">2894989000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20181231"
      decimals="-3"
      id="Fact_bacec939ac84418cbf35df017212761d"
      unitRef="U002">2667784000</us-gaap:Assets>
    <us-gaap:AccountsPayableCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_e36e66d0552f404099023f535d194dfe"
      unitRef="U002">13146000</us-gaap:AccountsPayableCurrent>
    <us-gaap:AccountsPayableCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_0c0b6424e746450abd937b9f839aed88"
      unitRef="U002">28660000</us-gaap:AccountsPayableCurrent>
    <us-gaap:EmployeeRelatedLiabilitiesCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_552968f4f2a9496e83f175a2ee89b95c"
      unitRef="U002">24404000</us-gaap:EmployeeRelatedLiabilitiesCurrent>
    <us-gaap:EmployeeRelatedLiabilitiesCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_e06d0b21026d4d1db2ff5f69431f6629"
      unitRef="U002">29268000</us-gaap:EmployeeRelatedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_2fefcdea93734fcd9274bd7403d639f5"
      unitRef="U002">52615000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_213f5a6701c24aa0979bad8e60ab97c3"
      unitRef="U002">47503000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedIncomeTaxesCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_2af0ce9cd98b44bd81fc94205bb5c219"
      unitRef="U002">1945000</us-gaap:AccruedIncomeTaxesCurrent>
    <us-gaap:AccruedIncomeTaxesCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_7acc385f5ade40c4a52676f52d77facb"
      unitRef="U002">858000</us-gaap:AccruedIncomeTaxesCurrent>
    <us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_bfee8ed3f29a415ba60a766b5e0cc4b7"
      unitRef="U002">2060000</us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent>
    <us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_41e0bc055640457ebe9012a9d8313b03"
      unitRef="U002">13749000</us-gaap:LongTermDebtAndCapitalLeaseObligationsCurrent>
    <us-gaap:ContractWithCustomerLiabilityCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_09d676ed2f6648e5b73076a656df1277"
      unitRef="U002">137607000</us-gaap:ContractWithCustomerLiabilityCurrent>
    <us-gaap:ContractWithCustomerLiabilityCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_0b483c68b6994735bd21436d4b811df6"
      unitRef="U002">160256000</us-gaap:ContractWithCustomerLiabilityCurrent>
    <us-gaap:LiabilitiesCurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_b563c92d4e8b4add87b63f57c52a0e82"
      unitRef="U002">231777000</us-gaap:LiabilitiesCurrent>
    <us-gaap:LiabilitiesCurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_d521a592d7c446a7b398adb17b375e32"
      unitRef="U002">280294000</us-gaap:LiabilitiesCurrent>
    <us-gaap:ContractWithCustomerLiabilityNoncurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_8aa6408241e44715ba99551864adcae8"
      unitRef="U002">492979000</us-gaap:ContractWithCustomerLiabilityNoncurrent>
    <us-gaap:ContractWithCustomerLiabilityNoncurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_ede8dfed22c34e9582c277c64ee5a671"
      unitRef="U002">567359000</us-gaap:ContractWithCustomerLiabilityNoncurrent>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20181231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_bbd023eee50e42438aa37192e3fb599a"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_3d6e1ab8d0ea4dfca582273a77b28bd5"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ConvertibleDebtNoncurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_74ce7adcfde44543a313ce009163795e"
      unitRef="U002">596355000</us-gaap:ConvertibleDebtNoncurrent>
    <us-gaap:ConvertibleDebtNoncurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_18f77ca1d76f433882b17b855d930dd6"
      unitRef="U002">568215000</us-gaap:ConvertibleDebtNoncurrent>
    <ions:LongTermObligationsNoncurrent
      contextRef="c20190930"
      decimals="-3"
      id="Fact_29af6f780a0e49fdbb18e694cd1336d7"
      unitRef="U002">16016000</ions:LongTermObligationsNoncurrent>
    <ions:LongTermObligationsNoncurrent
      contextRef="c20181231"
      decimals="-3"
      id="Fact_633c4e81bd56468da5eab170b086f121"
      unitRef="U002">4914000</ions:LongTermObligationsNoncurrent>
    <us-gaap:LongTermLoansFromBank
      contextRef="c20190930"
      decimals="-3"
      id="Fact_47ee861cba2b4ba3b4ea02fec4ccb666"
      unitRef="U002">59896000</us-gaap:LongTermLoansFromBank>
    <us-gaap:LongTermLoansFromBank
      contextRef="c20181231"
      decimals="-3"
      id="Fact_aa0760afbb9c4732aa47a17bbf801618"
      unitRef="U002">59842000</us-gaap:LongTermLoansFromBank>
    <us-gaap:Liabilities
      contextRef="c20190930"
      decimals="-3"
      id="Fact_d80c046b930b4bbc9a617d5de07fbac7"
      unitRef="U002">1397023000</us-gaap:Liabilities>
    <us-gaap:Liabilities
      contextRef="c20181231"
      decimals="-3"
      id="Fact_90063554b014412d8b997e613766a9b5"
      unitRef="U002">1480624000</us-gaap:Liabilities>
    <us-gaap:CommonStockParOrStatedValuePerShare
      contextRef="c20181231"
      decimals="3"
      id="Fact_89ceac2a6de84664a3444e0197c5952f"
      unitRef="U004">0.001</us-gaap:CommonStockParOrStatedValuePerShare>
    <us-gaap:CommonStockParOrStatedValuePerShare
      contextRef="c20190930"
      decimals="3"
      id="Fact_81d34c4177db42eb9566a4ebacfe9a61"
      unitRef="U004">0.001</us-gaap:CommonStockParOrStatedValuePerShare>
    <us-gaap:CommonStockSharesAuthorized
      contextRef="c20181231"
      decimals="0"
      id="Fact_c1d115fce5ca4643b306e1dda169e403"
      unitRef="U001">300000000</us-gaap:CommonStockSharesAuthorized>
    <us-gaap:CommonStockSharesAuthorized
      contextRef="c20190930"
      decimals="0"
      id="Fact_967e3bfa845149deb2a16ff5f6733824"
      unitRef="U001">300000000</us-gaap:CommonStockSharesAuthorized>
    <us-gaap:CommonStockSharesOutstanding
      contextRef="c20190930"
      decimals="0"
      id="Fact_7433a63c4a1045d2ab18a5f4dd2cfef3"
      unitRef="U001">140636397</us-gaap:CommonStockSharesOutstanding>
    <us-gaap:CommonStockSharesIssued
      contextRef="c20190930"
      decimals="0"
      id="Fact_aeabe9bc47984305a06e132d4d7bbbd3"
      unitRef="U001">140636397</us-gaap:CommonStockSharesIssued>
    <us-gaap:CommonStockSharesOutstanding
      contextRef="c20181231"
      decimals="0"
      id="Fact_16b1e67a7f564bfb8ebe67a950cecb91"
      unitRef="U001">137928828</us-gaap:CommonStockSharesOutstanding>
    <us-gaap:CommonStockSharesIssued
      contextRef="c20181231"
      decimals="0"
      id="Fact_987e70eb15fa4d6f8f4dee73a63054d5"
      unitRef="U001">137928828</us-gaap:CommonStockSharesIssued>
    <us-gaap:CommonStockValue
      contextRef="c20190930"
      decimals="-3"
      id="Fact_b41f780321ff493f897af65f3a6e39be"
      unitRef="U002">141000</us-gaap:CommonStockValue>
    <us-gaap:CommonStockValue
      contextRef="c20181231"
      decimals="-3"
      id="Fact_1fc75883a1c54dde89dbf7d834d50fb8"
      unitRef="U002">138000</us-gaap:CommonStockValue>
    <us-gaap:AdditionalPaidInCapitalCommonStock
      contextRef="c20190930"
      decimals="-3"
      id="Fact_f460fecc10794c159f5558f0e607190e"
      unitRef="U002">2219090000</us-gaap:AdditionalPaidInCapitalCommonStock>
    <us-gaap:AdditionalPaidInCapitalCommonStock
      contextRef="c20181231"
      decimals="-3"
      id="Fact_11b21d76e415443eacd46443135bee23"
      unitRef="U002">2047250000</us-gaap:AdditionalPaidInCapitalCommonStock>
    <us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax
      contextRef="c20190930"
      decimals="-3"
      id="Fact_0fa166eb9bd4465a9b655bbddbbc9660"
      unitRef="U002">-25375000</us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax>
    <us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax
      contextRef="c20181231"
      decimals="-3"
      id="Fact_aaa97c5af992480997806ad6ed39c8b8"
      unitRef="U002">-32016000</us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax>
    <us-gaap:RetainedEarningsAccumulatedDeficit
      contextRef="c20190930"
      decimals="-3"
      id="Fact_b87fd4221ecc4c9dbc01611589c1f02d"
      unitRef="U002">-857563000</us-gaap:RetainedEarningsAccumulatedDeficit>
    <us-gaap:RetainedEarningsAccumulatedDeficit
      contextRef="c20181231"
      decimals="-3"
      id="Fact_70969fab8ec04e7583d69d70666445de"
      unitRef="U002">-967293000</us-gaap:RetainedEarningsAccumulatedDeficit>
    <us-gaap:StockholdersEquity
      contextRef="c20190930"
      decimals="-3"
      id="Fact_f7df6d935cfc498584c42c103121920f"
      unitRef="U002">1336293000</us-gaap:StockholdersEquity>
    <us-gaap:StockholdersEquity
      contextRef="c20181231"
      decimals="-3"
      id="Fact_796dd0d0c977460fa5f2ab16e5545e4b"
      unitRef="U002">1048079000</us-gaap:StockholdersEquity>
    <us-gaap:MinorityInterest
      contextRef="c20190930"
      decimals="-3"
      id="Fact_0e8547099dcc477d9574551822f8c2cc"
      unitRef="U002">161673000</us-gaap:MinorityInterest>
    <us-gaap:MinorityInterest
      contextRef="c20181231"
      decimals="-3"
      id="Fact_5ab17487f86d49fa8f57d80fc26134da"
      unitRef="U002">139081000</us-gaap:MinorityInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930"
      decimals="-3"
      id="Fact_19cb4d43fab24662ad8de75f93f0f483"
      unitRef="U002">1497966000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231"
      decimals="-3"
      id="Fact_6951ed54246642938032f494c08fdf05"
      unitRef="U002">1187160000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:LiabilitiesAndStockholdersEquity
      contextRef="c20190930"
      decimals="-3"
      id="Fact_134e1347f8c347aab0132349b4784b81"
      unitRef="U002">2894989000</us-gaap:LiabilitiesAndStockholdersEquity>
    <us-gaap:LiabilitiesAndStockholdersEquity
      contextRef="c20181231"
      decimals="-3"
      id="Fact_49524665a65e4e5db0c98d6bb79422df"
      unitRef="U002">2667784000</us-gaap:LiabilitiesAndStockholdersEquity>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_0b7e92ae84094d37aed4349f19fe764e"
      unitRef="U002">81672000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_82fd59906fb44bf4b175b6e556a27aac"
      unitRef="U002">70010000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_fc05c9c21bbd4d598e399567bd0f844d"
      unitRef="U002">211884000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_9e31bec432124f7c8f83a4f356e361da"
      unitRef="U002">167743000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_666782232adc4d97b1de7acd7fe4af26"
      unitRef="U002">11945000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_6d53ba73214c4912b0f063f1483c62c1"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_c692e5012c26423f8d5dbd3a8094950e"
      unitRef="U002">28563000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_3fbd588a01cd48839b4bfc40a134670e"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_5be3788d99f54fdfaee577a7cda5700b"
      unitRef="U002">2082000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_0347f12cd3584a27a5619a2467dd39b0"
      unitRef="U002">12746000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_2ca205ab66e94f488dbfed885dd2ec26"
      unitRef="U002">11638000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_1e01b330b4b0472c9250121ed807739a"
      unitRef="U002">14232000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_271ba182566f4bc190d8233a71995d31"
      unitRef="U002">95699000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_11a881c1e93e430eac6f59cbf9c4736b"
      unitRef="U002">82756000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_3390343e9af54d66a37bc2b71ebdada1"
      unitRef="U002">252085000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_ea548ed659af43b48bb282d83609fa0b"
      unitRef="U002">181975000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_8fd333eb68924256a711503ecfe6689a"
      unitRef="U002">72193000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_19de1dac977a4ba5974be8c2aac9440b"
      unitRef="U002">62639000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_fa04642ad0d24d40b948016a1d2e427c"
      unitRef="U002">376833000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_b5f0d20ca299467388d20dd594b8c246"
      unitRef="U002">225584000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_fc7abdc8dfde471cb29faf8b3d03b1e5"
      unitRef="U002">167892000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_d18c45e0616c4b608bc566221c7d5133"
      unitRef="U002">145395000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_ea3d788d8e4c4ca49f0e56246a6353d6"
      unitRef="U002">628918000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_946194dd265d4cea91b3510e10eec2e5"
      unitRef="U002">407559000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:CostOfGoodsAndServicesSold
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_c4ea9d289db04074bad2be0b780555ef"
      unitRef="U002">967000</us-gaap:CostOfGoodsAndServicesSold>
    <us-gaap:CostOfGoodsAndServicesSold
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_3f378c9d048d4d0abe6a570fd9323df7"
      unitRef="U002">0</us-gaap:CostOfGoodsAndServicesSold>
    <us-gaap:CostOfGoodsAndServicesSold
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_c2742b31d05445a1895276df6ff2c638"
      unitRef="U002">3373000</us-gaap:CostOfGoodsAndServicesSold>
    <us-gaap:CostOfGoodsAndServicesSold
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_dbe88d486cf14375a9f138d6c30834d5"
      unitRef="U002">0</us-gaap:CostOfGoodsAndServicesSold>
    <ions:ResearchDevelopmentAndPatentExpense
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_a9acfc8017e7443cadb09efb73dd40aa"
      unitRef="U002">104366000</ions:ResearchDevelopmentAndPatentExpense>
    <ions:ResearchDevelopmentAndPatentExpense
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_5ec7677070de41efba668575300cbc3b"
      unitRef="U002">95255000</ions:ResearchDevelopmentAndPatentExpense>
    <ions:ResearchDevelopmentAndPatentExpense
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_6c53d68927644fc5908dc607a0f004fb"
      unitRef="U002">316948000</ions:ResearchDevelopmentAndPatentExpense>
    <ions:ResearchDevelopmentAndPatentExpense
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_aadd9a4a9b6e45d396e8e9c8d975c3a8"
      unitRef="U002">301153000</ions:ResearchDevelopmentAndPatentExpense>
    <us-gaap:SellingGeneralAndAdministrativeExpense
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_88509240b8f44a01a221693c1c02bb2a"
      unitRef="U002">60036000</us-gaap:SellingGeneralAndAdministrativeExpense>
    <us-gaap:SellingGeneralAndAdministrativeExpense
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_16ecfb44722848e38992eb9ca9030a3f"
      unitRef="U002">68712000</us-gaap:SellingGeneralAndAdministrativeExpense>
    <us-gaap:SellingGeneralAndAdministrativeExpense
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_054cd1ab95374ebd8869d776879a9740"
      unitRef="U002">203368000</us-gaap:SellingGeneralAndAdministrativeExpense>
    <us-gaap:SellingGeneralAndAdministrativeExpense
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_2ff4a991cea4496b884cbe0856914388"
      unitRef="U002">178563000</us-gaap:SellingGeneralAndAdministrativeExpense>
    <us-gaap:CostsAndExpenses
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_2475cd3acfd24e6cbbc308e4c9e591b9"
      unitRef="U002">165369000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_ad210a86a31a424e9965b4608c3fe4e5"
      unitRef="U002">163967000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_aa6c4d98b6394cbe8ccd0ee6c8cebd19"
      unitRef="U002">523689000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_4fbf0fcf0f4142b1b4afedb23bae57ad"
      unitRef="U002">479716000</us-gaap:CostsAndExpenses>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_bee2844586ba438c8e913f61b67d695a"
      unitRef="U002">2523000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_0c2223c913e04fa7a54624202a8f288f"
      unitRef="U002">-18572000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_76aedfc468a64cb7aef3f084651fb9b9"
      unitRef="U002">105229000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_d1d46d66a90149e5b13f260102617cfd"
      unitRef="U002">-72157000</us-gaap:OperatingIncomeLoss>
    <us-gaap:InvestmentIncomeNet
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_66c58aa0cc1149b793eab1f8666cea91"
      unitRef="U002">13136000</us-gaap:InvestmentIncomeNet>
    <us-gaap:InvestmentIncomeNet
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_f1678e81b9bb4a9d973cf0e5d0aa3275"
      unitRef="U002">9963000</us-gaap:InvestmentIncomeNet>
    <us-gaap:InvestmentIncomeNet
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_0d64264f32b4486b894513e64aff02d3"
      unitRef="U002">39015000</us-gaap:InvestmentIncomeNet>
    <us-gaap:InvestmentIncomeNet
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_cbd13fb3278b42f4af046675f6407585"
      unitRef="U002">18711000</us-gaap:InvestmentIncomeNet>
    <us-gaap:InterestExpense
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_54aac10cb0064fbe92e0fba8afd6804a"
      unitRef="U002">12002000</us-gaap:InterestExpense>
    <us-gaap:InterestExpense
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_718aef5f4e5c47ed993b6dc62100e496"
      unitRef="U002">11282000</us-gaap:InterestExpense>
    <us-gaap:InterestExpense
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_2e8326e1dfff4b1ea6081f53587960f9"
      unitRef="U002">35404000</us-gaap:InterestExpense>
    <us-gaap:InterestExpense
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_99b07d066f7e4ca98c5bff25af703b10"
      unitRef="U002">33332000</us-gaap:InterestExpense>
    <us-gaap:OtherNonoperatingIncomeExpense
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_01fdf07252e54f319cb90db79a32d5d0"
      unitRef="U002">-140000</us-gaap:OtherNonoperatingIncomeExpense>
    <us-gaap:OtherNonoperatingIncomeExpense
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_1175fa808fa6467fa69c45f4c6ffb802"
      unitRef="U002">-22000</us-gaap:OtherNonoperatingIncomeExpense>
    <us-gaap:OtherNonoperatingIncomeExpense
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_14d3f9e37db043e9b6e9051b02cb728d"
      unitRef="U002">-332000</us-gaap:OtherNonoperatingIncomeExpense>
    <us-gaap:OtherNonoperatingIncomeExpense
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_fa874df28ad34f8db61bd85baa7b2b8f"
      unitRef="U002">-145000</us-gaap:OtherNonoperatingIncomeExpense>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_4e15511699034f4d9b1ebe90cebb3ff3"
      unitRef="U002">3517000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_ae656811157844b5ba3ea60d95c6c011"
      unitRef="U002">-19913000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_96b769f3a1e94075b08c9a9c0a99b7ab"
      unitRef="U002">108508000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_0fd4ef6b1fc94874a6d21469662158c7"
      unitRef="U002">-86923000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_8ce8cdd30acf4bbc839e7536c1a25e45"
      unitRef="U002">-14915000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_391c23bb87034306903c5e329f247717"
      unitRef="U002">452000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_69f39ebeb04d480ba5b5698dbb3a8275"
      unitRef="U002">9204000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_4ce3fbd20b7e46459a27754ecad5863a"
      unitRef="U002">824000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:ProfitLoss
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_6e839ad01bca473db272756ca24f0c6c"
      unitRef="U002">18432000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_4a3cf63ebc8c4917ba22720d153c34e6"
      unitRef="U002">-20365000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_a05a0daeca784f1085c298eda7c00b97"
      unitRef="U002">99304000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_0fbef789f1334a9086f868678bb389ab"
      unitRef="U002">-87747000</us-gaap:ProfitLoss>
    <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_9880bcb6013f487caf2824136dbb2aad"
      unitRef="U002">-7732000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_032762f55fd243a6b68fb4543524a1d8"
      unitRef="U002">-15806000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_d57908ccdd8247a382987a2800dacce3"
      unitRef="U002">-10426000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLossAttributableToNoncontrollingInterest
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_bf4aef66191d47af85daec16883e4386"
      unitRef="U002">-41412000</us-gaap:NetIncomeLossAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_e3073c5f38e04ff596a4331d93107ae6"
      unitRef="U002">26163000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_b31821fc458d431999aec86855835cd4"
      unitRef="U002">-4559000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_3337df5280e143d4bf6b2ee0bc26ca21"
      unitRef="U002">109730000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_b83dbcd82d4846cdbdbb049adc53fbe8"
      unitRef="U002">-46335000</us-gaap:NetIncomeLoss>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190701to20190930"
      decimals="2"
      id="Fact_5fc4c4e19798409a922b541c2e74e551"
      unitRef="U004">0.19</us-gaap:EarningsPerShareBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20180701to20180930"
      decimals="2"
      id="Fact_3a0c2f544ba54492bba4f602b2c20f5c"
      unitRef="U004">-0.03</us-gaap:EarningsPerShareBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190101to20190930"
      decimals="2"
      id="Fact_87f607dd11724c82a75bf67ec6bc0726"
      unitRef="U004">0.81</us-gaap:EarningsPerShareBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20180101to20180930"
      decimals="2"
      id="Fact_ebc5b8c1d1774c90a2eed601a46d5092"
      unitRef="U004">-0.33</us-gaap:EarningsPerShareBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_413750ca99dd490aabc1f5ce044c7bd2"
      unitRef="U001">140551000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_89ae87d3ce154c29b80ab797905a4335"
      unitRef="U001">137346000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_cf5a3286afeb4ba091732f9659f005a0"
      unitRef="U001">139800000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_86db24f4e52b47c3ae8b79a4eee6c5a7"
      unitRef="U001">130507000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20190701to20190930"
      decimals="2"
      id="Fact_de8dfc22ca3346229ea5ae768a2fae60"
      unitRef="U004">0.18</us-gaap:EarningsPerShareDiluted>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20180701to20180930"
      decimals="2"
      id="Fact_a6389f538da2442cbfd16ab66ce3ba4e"
      unitRef="U004">-0.03</us-gaap:EarningsPerShareDiluted>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20190101to20190930"
      decimals="2"
      id="Fact_540ef4013fa04ee6a485bb76536d6f72"
      unitRef="U004">0.79</us-gaap:EarningsPerShareDiluted>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20180101to20180930"
      decimals="2"
      id="Fact_e9745ef5d64d4dcb82f0afe9ae660902"
      unitRef="U004">-0.33</us-gaap:EarningsPerShareDiluted>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_d49d301e3cc945869aec44ece6cbad37"
      unitRef="U001">143408000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_bf0aedc97af44714af5336a371515cc8"
      unitRef="U001">137346000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_f48d610147fa4ae1a37ac7a3d9e37c31"
      unitRef="U001">142821000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_e8ed2d920fd0439b9a5d8732eec0f5ff"
      unitRef="U001">130507000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:ProfitLoss
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_956abcf640b64e40a411493d69205818"
      unitRef="U002">18432000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_47e41b95caab4e92bb28995bd44b3aad"
      unitRef="U002">-20365000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_8300a6f66bfe443db38d77ca66f51505"
      unitRef="U002">99304000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_23d6e30666fb4b788e6dd4f69f822c31"
      unitRef="U002">-87747000</us-gaap:ProfitLoss>
    <us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_55347736030740569e680a5e37637b63"
      unitRef="U002">-1110000</us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_d74b567e3b014156a049c64e1307a63a"
      unitRef="U002">133000</us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_a0e0ce1af3e4453cb56c625c0c8f2800"
      unitRef="U002">6666000</us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_a5e1f7fa552a425a9c7bfb376af815b6"
      unitRef="U002">-834000</us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_e9b531ac4e7e466f809b4e8a0d95361e"
      unitRef="U002">-13000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_b162ec084f6c46ccaef6685d9c1854ba"
      unitRef="U002">-31000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_a20a0cc52121458bb55a81fdd00e75b7"
      unitRef="U002">-25000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_daa1a7f93f5945139be6141a4e1ef612"
      unitRef="U002">61000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_f0bdb8167ba5440599f8ff8f4600c9fe"
      unitRef="U002">17309000</us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_1d9694905eb840a7a1ca80fb0815c33e"
      unitRef="U002">-20263000</us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_be0067f854be45bf95bdf2c489e2d13e"
      unitRef="U002">105945000</us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_f317117367b0435c862ef7858aad4a56"
      unitRef="U002">-88520000</us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_a269dc621aa04d119bef4f51cfd30b55"
      unitRef="U002">-7729000</us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_8cb081eaec8d4a1ba90652e3efc63cd6"
      unitRef="U002">-13943000</us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_6ae3051280094a839a54335e64d62821"
      unitRef="U002">-10423000</us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_1605d18c25544e4a82d222c9f7bc9a9b"
      unitRef="U002">-38005000</us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest>
    <us-gaap:ComprehensiveIncomeNetOfTax
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_065f79ada0374820bc5a6fbec88a7615"
      unitRef="U002">25038000</us-gaap:ComprehensiveIncomeNetOfTax>
    <us-gaap:ComprehensiveIncomeNetOfTax
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_7959aba910af49989a21445262c14dde"
      unitRef="U002">-6320000</us-gaap:ComprehensiveIncomeNetOfTax>
    <us-gaap:ComprehensiveIncomeNetOfTax
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_4ef4b46b1e6548a9989d6308f38d02ec"
      unitRef="U002">116368000</us-gaap:ComprehensiveIncomeNetOfTax>
    <us-gaap:ComprehensiveIncomeNetOfTax
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_d9ab0bf4afe247139adf3c7fd48dcc8f"
      unitRef="U002">-50515000</us-gaap:ComprehensiveIncomeNetOfTax>
    <us-gaap:SharesIssued
      contextRef="c20180630_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_bceab59188424c15adeaa4abc2b75b2c"
      unitRef="U001">137157000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_f88139526b6546c0a62ece28db065504"
      unitRef="U002">137000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_78cf6c31b63d4529a7b11529d0d3fac7"
      unitRef="U002">2011561000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_47ae58c233e44842bafc4d977a4aa088"
      unitRef="U002">-32634000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_7c0e43df67e14da49a468b8edca8b7ed"
      unitRef="U002">-1282810000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_6c3bdff0323a479bbc545417e99af981"
      unitRef="U002">696254000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_596d88f5d89942a69c32fb0dc5d059e3"
      unitRef="U002">121181000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180630"
      decimals="-3"
      id="Fact_c06694f9fb0b4755a570468320903574"
      unitRef="U002">817436000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_9fc566f7fda04ae5a5c8ea2305bdf298"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_bb24e7d634c44db38ea3ffa53ac03797"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_e9359509cd5a439e82e79b016c1fab7f"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_4b4f5c2aabf34cefaa88539842c518da"
      unitRef="U002">-4559000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_156717fab30449c1b5eacac23304af91"
      unitRef="U002">-4559000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_44a7c5e4da9e43f09944151b7a453391"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_3158a0f067284faeb554dcb4f6ce5ef2"
      unitRef="U002">-4559000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_593e345ebaae46dbb963d490969b01b6"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_eac9065025fe450a9a08f92abe49d5ca"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_f4951a777dc447b58af150fdb4dca2fa"
      unitRef="U002">133000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_7a2b7d1f5d4b4cf2b6bbdf306650d93d"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_95d55e206caa47b1a446bf9db36d287c"
      unitRef="U002">133000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_2965ef559b3c4d84ae8ecd3e0783ff50"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_b214c0c8476b4d219a6cf92692b53f88"
      unitRef="U002">133000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_e29f8ebcc2f0483a9440f01323ea3e11"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_821accc58f9145f3b1740e74ff0af16f"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_bacfd0c31c3e429391016b2bc472d382"
      unitRef="U002">-31000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_fd2bb27765944367b3078298024899ee"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_a439436ef2774a7985521c51bf62a03d"
      unitRef="U002">-31000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_0cf82e5935704d11904efa4267b6229e"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_6360ce93a0d54280815c7e432aade2fb"
      unitRef="U002">-31000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_6630c3118460436bbf1c06d6a34339a9"
      unitRef="U001">350000</us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_d0613d6c586e49feab72a616948801dd"
      unitRef="U002">1000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_bcaabce92e8c4b049a180be9f31b22b7"
      unitRef="U002">6225000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_160dcfb2e3604ff18da92958b3968a96"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_622dec14e7144a7eb02667f5a97c5d4d"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_6c42499de554402280d3775bbcb588e1"
      unitRef="U002">6226000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_cece69af14014498bac2170ea2e6bb21"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_c195541964b64957ab73cf1bb9a796b8"
      unitRef="U002">6226000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_e594b0c960034095b7b3afeadd852b0a"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_dd989a94a7a3414f9c8d9c9ccef76384"
      unitRef="U002">34883000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_90a5d787057f4caf8a9a856ebe4799df"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_7729530f9b3e46f99d9cd96a62e77f46"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_6fca89d1d55c45c49c8b5fc3cab33865"
      unitRef="U002">34883000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_73c9bef265c84f2ca25fe41b10ad1848"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_c43231f29342428cac3c21af502b0587"
      unitRef="U002">34883000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_7db5e110c8f542198fa1a9d98f2559d0"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_a8fbcc1325854db9b27c5f5bf123a6de"
      unitRef="U002">-22356000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_6a8c78038f9746599fc7080366c7863c"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_c990b70a9c6f4f6caed4b0586e87d0f1"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_bf6523db1d824d7f81b4b9893185bcb8"
      unitRef="U002">-22356000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_66c2c13181c74f3598876394d0f48fef"
      unitRef="U002">8413000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_32db0f97c7cd4f0da0e74967e15dcbe1"
      unitRef="U002">-13943000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:SharesIssued
      contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_c3359d08af2e4d5ea198fa0fd127edac"
      unitRef="U001">137507000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_6dde8ef0d2274f8082c6fad9e0e45d69"
      unitRef="U002">138000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_ba25a26602644681afcfb523a2e79289"
      unitRef="U002">2030313000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_6cad5f602ba146659c07b7ce82fd3a23"
      unitRef="U002">-32532000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_79b5bf319fb54532a598cba9b7b244cb"
      unitRef="U002">-1287369000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_ff395584dab641a18e3d808cd3e62b10"
      unitRef="U002">710550000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_f9b7ab5b4a8d4ff1a0501b9ea436e6b1"
      unitRef="U002">129594000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930"
      decimals="-3"
      id="Fact_d59c9e81ea9149f7a486f4c99ab791fe"
      unitRef="U002">840144000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:SharesIssued
      contextRef="c20190630_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_c60478aa8c15459f8a7bbd6caa1c8895"
      unitRef="U001">140393000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_8bfe81137d574448a15e3e272d041aaa"
      unitRef="U002">140000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_35a91c6a829b43e4aae11e23e41334f5"
      unitRef="U002">2177222000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_abcd350357194091be5dbe1cd4160111"
      unitRef="U002">-24252000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_3895fbc3ceaa44dd830723f29b4105b0"
      unitRef="U002">-883726000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_29f527152e394382bbffa3e986ef04b8"
      unitRef="U002">1269384000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_e29db74b7cef4543bd7e91be4d62c616"
      unitRef="U002">187818000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190630"
      decimals="-3"
      id="Fact_a891962649e6426d86f6ad7bf0373521"
      unitRef="U002">1457202000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_977eba342ad24a3298769cc096cf3e75"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_dd0a32f839f34b2391027fb60a50462e"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_e28dd2aa6b874e569198b6d4d54ef424"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_cfeb877b251a48a7b6cf29adc2f5e57d"
      unitRef="U002">26163000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_0626ae4513944b6c8712a96434792f82"
      unitRef="U002">26163000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_412fecf833154f7abf690541b132378a"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_c7d8d7c4c5d54ac2ba9ed007b8dd258f"
      unitRef="U002">26163000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_172ac55e7b5a498eb599d2d8f8eec47e"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_1867eac944aa41cbae8e3d47abc3d6a7"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_6b57ae9c250e47baa4e97986aadf8c81"
      unitRef="U002">-1110000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_da9d5f151eda4dbcb0bcb75e34a22be4"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_0e0eb1754a8d492691ca654fbbe6eae1"
      unitRef="U002">-1110000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_3377027aedf145e2a62b53af92fe76b0"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_854b5b7c73ce47748903f3a041b0888a"
      unitRef="U002">-1110000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_29321b0ef52149f9a102167ff8a99b50"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_48560808d032489896d62d1382c76f1e"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_483544f2c05f44ac8b9872662574f3fb"
      unitRef="U002">-13000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_428691c0d8a34530b8ff0a8c41b7850e"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_34958569cbc1462599bcc3ca090dff9b"
      unitRef="U002">-13000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_b58932b1827b438fae35d1b25e1d4b74"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_2875fd9f4ab5400dbf518756023a110c"
      unitRef="U002">-13000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_a026a55810e04bb19308f26ab420ad4d"
      unitRef="U001">255000</us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_39226d96f9604378aed335553da74ceb"
      unitRef="U002">1000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_5f19ce07c41a4e06960e938a80b50a33"
      unitRef="U002">10130000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_e3b43b28e23c49b8a85c08b6756cf9f0"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_8dfb0d6d1c6e428981aac693f68adbf1"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_da1411573bac461193f714edb592a68a"
      unitRef="U002">10131000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_fdd5b1db910a4419b75154b217f64127"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_8933da663a174dc586e754f61e39c7dc"
      unitRef="U002">10131000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_1b1b261601134ad7b527b00058348fe4"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_69d1f2603695493eb1510e71ac3bbc9b"
      unitRef="U002">24126000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_951d56bad286435ba8a2246e3e2d423f"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_d21e58738a734502b5f78fb4d2bdef0f"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_810d53dec70a43e0be887b6141deca77"
      unitRef="U002">24126000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_d9533d71316e44099bc2f2fc6e477a40"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_b9ff5349bf714543a98ce3f88e119830"
      unitRef="U002">24126000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_5fe714273c30499c9e486064f7b4b5dd"
      unitRef="U001">11000</us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_f79726916e124c468d0230aa19c54f11"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_38c35f2c742f433fb8fa53a4fdef9972"
      unitRef="U002">10804000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_04539bb1ef754c67ad7a831b15058953"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_6fa83dcbf2634d7eb7d376df35e1b8d3"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_42df54577138410faaad61b92b513286"
      unitRef="U002">10804000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_dd76df29fa044ea5b2e058e956f56cc5"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_2aa42131140c47889666342fdce4bf37"
      unitRef="U002">10804000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_c86b430bc1b44672ab27e5ef879375cd"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_c237f66e96ba4ce5ab488ab071c5d276"
      unitRef="U002">18416000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_2dcfbc0f27804b5787e0e2b93fed5a17"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_d1f78ebc0abe40c0ac4b588df3b79a63"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_94f5913e46be43d18abc42a727c2dc4d"
      unitRef="U002">18416000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_65c8e4b39ae34632a51d0bf623f965d0"
      unitRef="U002">-26145000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_ccbca592ee4344dba45e227a44457aab"
      unitRef="U002">-7729000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:SharesIssued
      contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_8fa67994f6bf40e78d066e4f4dc98810"
      unitRef="U001">140637000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_6cf39b5f854044b78edcc8e335e70e92"
      unitRef="U002">141000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_55717b5d3d8d40ff8bfe4ffb62adea43"
      unitRef="U002">2219090000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_3351e5260ee04c229a9264288b31015a"
      unitRef="U002">-25375000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_bc6630cc82394fe0aad0e6a861d90412"
      unitRef="U002">-857563000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_b1d05ec6c8cc4347b88b9e4b4cc010bc"
      unitRef="U002">1336293000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_7228c3ff57384f839b30be32c8c414a6"
      unitRef="U002">161673000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930"
      decimals="-3"
      id="Fact_57733ac2866b433db66897b885fa2359"
      unitRef="U002">1497966000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:SharesIssued
      contextRef="c20171231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_ddc7cf10a76f451c8b2b4aa0efe7c614"
      unitRef="U001">124976000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_a3737a74e2c84a07b526c4ecb1d4245c"
      unitRef="U002">125000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_55211c832be145c1bd2c207a06b16942"
      unitRef="U002">1553681000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_3dc283c48f254a9e93d024c1485b5603"
      unitRef="U002">-31759000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_4b1a649e5d604a8c96c1dcb1e3ad86bd"
      unitRef="U002">-1241034000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_6cf23cc0d1d5479c83f74cb58288d56d"
      unitRef="U002">281013000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_5c0eaf67f57a4bae8530de2dd3f33960"
      unitRef="U002">84267000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20171231"
      decimals="-3"
      id="Fact_a1a91a7e830b48eca3a86d4027d43049"
      unitRef="U002">365280000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_5ebcb96876e0459bb80e591552daef17"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_aa75c6042a6f439b8c2518d06d3bd5c9"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_67700f9c749f485a924b810c627d5fe2"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_4b2d05bdff834effa429f280a7d40614"
      unitRef="U002">-46335000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_b3ad397389ef4c399300993e8583e465"
      unitRef="U002">-46335000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_c202c415a5344cd0b6281508e66a4cc4"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_6f8bfb5eb2c340eda76b9c5c95c0ced0"
      unitRef="U002">-46335000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_e62b4a8dd22e492b934e39b29c3d5909"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_e2def5bf3b8443798c0862c0b7342249"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_7c0db743213f4c49b2ae444b04c7907b"
      unitRef="U002">-834000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_b6e9b195dc7940b1b8a4c59f4ef851ed"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_c1cfb7c5586445feaf54b3a96bb62c39"
      unitRef="U002">-834000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_176040219a764acb9fea4deb740d8a91"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_01ca9f1c819e4277af75bc9cef959535"
      unitRef="U002">-834000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_1f50a16d37a8423294c83b5ff8b38164"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_982a47fa8d3644dba1e623fb1c2c9476"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_7c2ff3b12307431ebedfab543a17940d"
      unitRef="U002">61000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_711f2f613200451fa72ee717ce0bbaaa"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_56f39bd775b844f7a307a9ce09c3c0fd"
      unitRef="U002">61000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_317f96be510f4c289a8be67492681848"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_330092d5cc7d401e8eba3233459a538a"
      unitRef="U002">61000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:StockIssuedDuringPeriodSharesNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_ee0b90d828ff40a3a175772f568db770"
      unitRef="U001">11502000</us-gaap:StockIssuedDuringPeriodSharesNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_7dab409285f142989e81e41b41aaf5cf"
      unitRef="U002">11000</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_a7067d24235942daa663277978ea22ae"
      unitRef="U002">447954000</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_1a08a50a788b4034a16580b56c3e38bc"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_e9d67aba016d4976bd285f3e402c73c1"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_ff428e47468f4e02814df9d8a5ada121"
      unitRef="U002">447965000</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_18b36961e78c489f88760e0d220758f8"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodValueNewIssues
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_336ebf4d394a4b42b647d3c11df0a9dc"
      unitRef="U002">447965000</us-gaap:StockIssuedDuringPeriodValueNewIssues>
    <us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_d1bdbcaa567441628c2ef5d1031fbf78"
      unitRef="U001">1029000</us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_be2452b0552b472aa17c5c8ec8461c32"
      unitRef="U002">2000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_d89629bda2d9446fb6deaafc29258ef4"
      unitRef="U002">14800000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_097668a314164bd188a8ad54ef3d10b4"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_4a997167d5d94d52b1fe66599f72e392"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_6152078c2e534c709c8a5c523907d682"
      unitRef="U002">14802000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_b7aa80aa648543b7b9b9e3619dd03f2b"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_b9871f32ecc34c30b7eb5dfa2bc8e69b"
      unitRef="U002">14802000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_b598c195eaf84d658146d068c0c83f78"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_431d4cae18b64b6a842b9d25d4549d53"
      unitRef="U002">97210000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_fb9af86803024908a001f5927e85d4b9"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_b3afeeeb5f3d4f898de60e54428d0de8"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_d4452c91b47547938b176b4e021434fe"
      unitRef="U002">97210000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_68a2f0a5e8a04829971f142a38882958"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_d946e571f77b4a4385127d499a8e13ea"
      unitRef="U002">97210000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_c60daf6058434e0fa0e2b6b6bab3b0a9"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_87b2eccc524b4103870bcd8158f0a9a4"
      unitRef="U002">-83332000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_09698d9fd4914c40ace49ec141ff6b80"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_f248e268d100429ba20f6264e206af32"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_3280d89dea3f4bd7ac4b9885cd77c30c"
      unitRef="U002">-83332000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_96890ae3e5cf4a06a144890989fe6042"
      unitRef="U002">45327000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_4ede0c53c9634a11bb27f7257027ef80"
      unitRef="U002">-38005000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:SharesIssued
      contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_4c7170dee1ec4920a29097e40c6ab19d"
      unitRef="U001">137507000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_454e18c51da34837a9d7820479c2e2e2"
      unitRef="U002">138000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_ab9738c203ec47169572bc2cbda0d754"
      unitRef="U002">2030313000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_50080ff24bd94948a26bd1fe84d2aa5b"
      unitRef="U002">-32532000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_fe662f9876344def8011a388c17f60d1"
      unitRef="U002">-1287369000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_5f92ae0c31b94956b30594a52a08f27a"
      unitRef="U002">710550000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_c04e5b991c1c40bf831f700f12239cfb"
      unitRef="U002">129594000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20180930"
      decimals="-3"
      id="Fact_2ed6745c19e8413195da23cac9b05937"
      unitRef="U002">840144000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:SharesIssued
      contextRef="c20181231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_fee7d7f5efaa4aa1b8c460e4a16ea7fb"
      unitRef="U001">137929000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_4df5adf4881a4a63aec3f101266b76d6"
      unitRef="U002">138000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_75ec3f39a822463791ea074e335a92f3"
      unitRef="U002">2047250000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_2029381cbce8449ba45e25f7de96225f"
      unitRef="U002">-32016000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_917b2ac712f14901b2e90a6d382fe009"
      unitRef="U002">-967293000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_9eed7c8ea3e9413dbcaaa1452e62a26b"
      unitRef="U002">1048079000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_8424068fab5b4bada989600c1d20bc4f"
      unitRef="U002">139081000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20181231"
      decimals="-3"
      id="Fact_af58a78c084e4e9e8a5ef2a3d3043c47"
      unitRef="U002">1187160000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_45123936bbd84866b03756a95d0c796d"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_15a72c452d2d43c8a14f170df416dfe3"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_da49e58b5dfb46d6888960e74b977b69"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_6885fdf2ef9441089e89c3277edd2591"
      unitRef="U002">109730000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_d535e4f71bd8461bb45bf7d0ef01492f"
      unitRef="U002">109730000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_7225c552985e49a09d45b0ce903f19dd"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_9f847706fda742779fcf3591ba87f390"
      unitRef="U002">109730000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_500d46c4bfca4212b740bccf33b982cc"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_e56ff1c2c77d49dda0fe1130a1e01fdd"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_263c693f37e24cb38ed834ecd9a652d1"
      unitRef="U002">6666000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_376fdc5e2d5b479ea2a236f157d5537c"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_00edfc6f60df4da0b41b16445549a176"
      unitRef="U002">6666000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_be58d9d656da4069ab0f9553b0fae185"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_402e37708d874b35b6711d1421373cf7"
      unitRef="U002">6666000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_88d9e3b7bb98403280070f245b2e8b16"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_3947e71e8b954b5c97775df046ed7d5a"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_d3d38dab3b754310b19a7c2ba5a82160"
      unitRef="U002">-25000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_65eae6716a2543ab84ed808dbe813a53"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_61d35598c2c94e1a9c0bf47d40a14425"
      unitRef="U002">-25000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_06e96816ce8f44d9b9861ac93493db4b"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_eab7b4251a5547059684440177dbb163"
      unitRef="U002">-25000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_bdb084067dec4e639732b2a241b4f0f4"
      unitRef="U001">2855000</us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_fc061deeaf414fb385fb62a5657f21ec"
      unitRef="U002">3000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_9fef205540764632be214acb5b9cec27"
      unitRef="U002">112132000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_42687c96437b45a39a73ddedbcd192fd"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_16e77799d06342409486a9c092f18725"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_d1952e003b8d42508f6df80dbd78c5d6"
      unitRef="U002">112135000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_b00270a3f4b64871a43c9a22da5d596b"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_8e9cf70e7e0c479ba9e68432d00c69d5"
      unitRef="U002">112135000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_9c4912015e674c42beba8d1fc969d3ee"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_7d344d4eb6a14d4792a4b9af3e43a874"
      unitRef="U002">111564000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_79187bc0728d40c9a40cce173e770f10"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_6b5b2407e2f547cbb7e191df8ff07107"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_f8b7027bc5ec4c8f9c7bce7ed24e53fe"
      unitRef="U002">111564000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_60c9c72ec2524b40a4692279e84fbf7e"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_a79a3e016e514b4cafe1a09d86429ac5"
      unitRef="U002">111564000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_b1c990bc0d3645be871f64f472db7c23"
      unitRef="U001">147000</us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_9fe5f5ef4d9f4a9cbaf1f12e625fcf6b"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_89d4bdca242243748410d19b1210e6b7"
      unitRef="U002">18841000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_ef5b034d8f964c1589c910467c9dafec"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_be5b1af1df45469ba696a14d825d9a47"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_4ab66a3a06724a9db9a232bd04e293f3"
      unitRef="U002">18841000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_3b4af19eaed34913a08a15ab82011ea5"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_4ed50e4cb7e540b681d94f7ddcd062dd"
      unitRef="U002">18841000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_5b3578f4d7a545c28e43ea47e3d4d7e1"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_d1f3c6f6ffce4dcd9171407be72f04d1"
      unitRef="U002">-33015000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_4bcf674568a64e19b059ec6ee03afa56"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_26db2a9d491b4ea48759ba7761540a05"
      unitRef="U002">0</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_48a0f306299d4ab7a051da51d2f25d28"
      unitRef="U002">-33015000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_9d99df3743a641f29215906163b79924"
      unitRef="U002">22592000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:MinorityInterestPeriodIncreaseDecrease
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_f26690d213024933b05ccf5cddbe7b1d"
      unitRef="U002">-10423000</us-gaap:MinorityInterestPeriodIncreaseDecrease>
    <us-gaap:SharesIssued
      contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_7cbfdbbb36ca464bae0814eda6c30402"
      unitRef="U001">140637000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_34f9ec06347a481c849caf2dea53db89"
      unitRef="U002">141000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_c5b0fe5c6e0b47fe8cbf429987d130ff"
      unitRef="U002">2219090000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_9d0d46e275464c3ebe27d823ecdb52a6"
      unitRef="U002">-25375000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_7a16ea3be1664c4ba9b0f21232a64560"
      unitRef="U002">-857563000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_ParentMember"
      decimals="-3"
      id="Fact_45103697ee8d4efa8832dff41ebbfa6d"
      unitRef="U002">1336293000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930_StatementEquityComponentsAxis_NoncontrollingInterestMember"
      decimals="-3"
      id="Fact_119a87edc2fa4ca8b2bef757fffd3fe2"
      unitRef="U002">161673000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20190930"
      decimals="-3"
      id="Fact_89506e267f834956b9ee7b9d8fb15786"
      unitRef="U002">1497966000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:ProfitLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_f7c36546ee144c2c86ebae7331367498"
      unitRef="U002">99304000</us-gaap:ProfitLoss>
    <us-gaap:ProfitLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_a21016941dc0429abc056d42872b32b2"
      unitRef="U002">-87747000</us-gaap:ProfitLoss>
    <us-gaap:Depreciation
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_100d69cecae84cbdad6e81cc7ef52262"
      unitRef="U002">9345000</us-gaap:Depreciation>
    <us-gaap:Depreciation
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_8c77ba4be59247e38c94131c141d0abf"
      unitRef="U002">7650000</us-gaap:Depreciation>
    <ions:OperatingLeaseRightOfUseAssetAmortization
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_9e6711269ac449af9f3ea5cf3d5eaa6a"
      unitRef="U002">1433000</ions:OperatingLeaseRightOfUseAssetAmortization>
    <ions:OperatingLeaseRightOfUseAssetAmortization
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_5558af291e4642f9823614e737f072ce"
      unitRef="U002">0</ions:OperatingLeaseRightOfUseAssetAmortization>
    <us-gaap:AmortizationOfIntangibleAssets
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_edc8ad178aa7466a8d83a15fca3ea881"
      unitRef="U002">1139000</us-gaap:AmortizationOfIntangibleAssets>
    <us-gaap:AmortizationOfIntangibleAssets
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_f8039ed914974946804216d314447463"
      unitRef="U002">1356000</us-gaap:AmortizationOfIntangibleAssets>
    <us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_246d1c45e9574034a56b56918f85ebb2"
      unitRef="U002">7064000</us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments>
    <us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_4aaed7ae1baf412b9dbc761309827e6d"
      unitRef="U002">-791000</us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_0996ae3cb47d4deda2a70a7fe98905e0"
      unitRef="U002">1448000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_0c9f58357fb646578e9fa6d8e42f1be2"
      unitRef="U002">1343000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:AmortizationOfDebtDiscountPremium
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_67a650ffc0ca4c9aae37011987ab83e5"
      unitRef="U002">26747000</us-gaap:AmortizationOfDebtDiscountPremium>
    <us-gaap:AmortizationOfDebtDiscountPremium
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_b0415b33ed664cbba8c9bfe200890e72"
      unitRef="U002">24781000</us-gaap:AmortizationOfDebtDiscountPremium>
    <us-gaap:ShareBasedCompensation
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_04aaa2990d5a40ad8fdb1b5232b70a08"
      unitRef="U002">111564000</us-gaap:ShareBasedCompensation>
    <us-gaap:ShareBasedCompensation
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_75990e27c7ef4862aef11ff7e8db6961"
      unitRef="U002">97210000</us-gaap:ShareBasedCompensation>
    <us-gaap:AssetImpairmentCharges
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_7fcd200b638b455db39131034fdc6876"
      unitRef="U002">216000</us-gaap:AssetImpairmentCharges>
    <us-gaap:AssetImpairmentCharges
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_fe5c9b55fb8549bebb24e58da0204a34"
      unitRef="U002">482000</us-gaap:AssetImpairmentCharges>
    <us-gaap:DeferredIncomeTaxExpenseBenefit
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_8414c778f38f421ba72eccd5272fd411"
      unitRef="U002">4103000</us-gaap:DeferredIncomeTaxExpenseBenefit>
    <us-gaap:DeferredIncomeTaxExpenseBenefit
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_21582d84c78941ef9bc300c0128beed5"
      unitRef="U002">0</us-gaap:DeferredIncomeTaxExpenseBenefit>
    <us-gaap:IncreaseDecreaseInContractWithCustomerAsset
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_16676ffc3ca64894b557287e56466f06"
      unitRef="U002">33716000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
    <us-gaap:IncreaseDecreaseInContractWithCustomerAsset
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_4adb47def1984cd7bbd6593823908452"
      unitRef="U002">-48223000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
    <us-gaap:IncreaseDecreaseInInventories
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_6cc57db037e24224babb23341491fa27"
      unitRef="U002">6606000</us-gaap:IncreaseDecreaseInInventories>
    <us-gaap:IncreaseDecreaseInInventories
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_855e538885814931adc2c6ca522196ff"
      unitRef="U002">-1604000</us-gaap:IncreaseDecreaseInInventories>
    <us-gaap:IncreaseDecreaseInOtherOperatingAssets
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_6beef6ad7156442b8b64be1683073767"
      unitRef="U002">23377000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
    <us-gaap:IncreaseDecreaseInOtherOperatingAssets
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_6b1b789ac55944df81d7f4361d13837c"
      unitRef="U002">26573000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
    <us-gaap:IncreaseDecreaseInAccountsPayable
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_8a994583ad564784b70d134601567caf"
      unitRef="U002">-18764000</us-gaap:IncreaseDecreaseInAccountsPayable>
    <us-gaap:IncreaseDecreaseInAccountsPayable
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_7d0b289b5d31478faec7c1781df64a2b"
      unitRef="U002">-13606000</us-gaap:IncreaseDecreaseInAccountsPayable>
    <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_5f5c568dfefd46649d7f965b7bc2f695"
      unitRef="U002">-4864000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
    <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_e29dcd8047ff491884c92796c96013cb"
      unitRef="U002">-892000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
    <ions:IncreaseDecreaseInAccruedAndDeferredLiabilities
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_08f6c9cf45f246f6a33cd0c9749cb737"
      unitRef="U002">3909000</ions:IncreaseDecreaseInAccruedAndDeferredLiabilities>
    <ions:IncreaseDecreaseInAccruedAndDeferredLiabilities
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_8da87902979a47b2b8cd9fcda264eef6"
      unitRef="U002">-14392000</ions:IncreaseDecreaseInAccruedAndDeferredLiabilities>
    <us-gaap:IncreaseDecreaseInContractWithCustomerLiability
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_5d444769c22d417199294bd747e46936"
      unitRef="U002">-97029000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
    <us-gaap:IncreaseDecreaseInContractWithCustomerLiability
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_7536a4e7a5c548658c9c6c4190e7e76b"
      unitRef="U002">447168000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
    <us-gaap:NetCashProvidedByUsedInOperatingActivities
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_66c31f18a56f439ab964f9bf11cd801d"
      unitRef="U002">67788000</us-gaap:NetCashProvidedByUsedInOperatingActivities>
    <us-gaap:NetCashProvidedByUsedInOperatingActivities
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_aaaa638d546d45448755c94c63222ccd"
      unitRef="U002">487398000</us-gaap:NetCashProvidedByUsedInOperatingActivities>
    <us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_083200534ca3433a9d3c58296e5b5402"
      unitRef="U002">1617726000</us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt>
    <us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_50e0b935822448d399c6da50df573ca5"
      unitRef="U002">1156335000</us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt>
    <us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_421423d1ea9a4d73aef63e7e59de4afb"
      unitRef="U002">1465600000</us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities>
    <us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_6dc4fafd64864e3188177206b20e21e5"
      unitRef="U002">568517000</us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities>
    <us-gaap:PaymentsToAcquirePropertyPlantAndEquipment
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_5c4c86b4988a4bcc93f568312cf27532"
      unitRef="U002">23143000</us-gaap:PaymentsToAcquirePropertyPlantAndEquipment>
    <us-gaap:PaymentsToAcquirePropertyPlantAndEquipment
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_23746708bcf2482183689f1b17ed01be"
      unitRef="U002">12221000</us-gaap:PaymentsToAcquirePropertyPlantAndEquipment>
    <ions:PaymentsToAcquireLicensesAndOtherAssets
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_bedfe0d50deb453aac9adee6a16b847b"
      unitRef="U002">4196000</ions:PaymentsToAcquireLicensesAndOtherAssets>
    <ions:PaymentsToAcquireLicensesAndOtherAssets
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_2503d109e9bf429abba6e180534abb50"
      unitRef="U002">3317000</ions:PaymentsToAcquireLicensesAndOtherAssets>
    <us-gaap:NetCashProvidedByUsedInInvestingActivities
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_92cb4d2048d14989a03cc74060fe995e"
      unitRef="U002">-179465000</us-gaap:NetCashProvidedByUsedInInvestingActivities>
    <us-gaap:NetCashProvidedByUsedInInvestingActivities
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_98c358a7d9cc4f7dbda064764db082d3"
      unitRef="U002">-603356000</us-gaap:NetCashProvidedByUsedInInvestingActivities>
    <us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_ddb0c2b46432418f9be1b92d0e804ae9"
      unitRef="U002">112137000</us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions>
    <us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_8bffc0bd215e4f839416df4a6531312e"
      unitRef="U002">18254000</us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions>
    <us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_b75a3de029544b8ea1fafba1be80eb98"
      unitRef="U002">18841000</us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_2013b605a8914f73b56ab03781e33c14"
      unitRef="U002">0</us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:ProceedsFromIssuanceOfCommonStock
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_debd829012124436b0de04a28fa90961"
      unitRef="U002">0</us-gaap:ProceedsFromIssuanceOfCommonStock>
    <us-gaap:ProceedsFromIssuanceOfCommonStock
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_54f753502f1e48f180c1bc730693f37d"
      unitRef="U002">447965000</us-gaap:ProceedsFromIssuanceOfCommonStock>
    <us-gaap:RepaymentsOfLongTermDebt
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_879a061318dd4c3eb2790021bc1151c3"
      unitRef="U002">12500000</us-gaap:RepaymentsOfLongTermDebt>
    <us-gaap:RepaymentsOfLongTermDebt
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_c0b4ad7116ba4f3db97cd83f155e9a38"
      unitRef="U002">0</us-gaap:RepaymentsOfLongTermDebt>
    <us-gaap:NetCashProvidedByUsedInFinancingActivities
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_eaaca3e288be4952adf9a7f8f7bf8f92"
      unitRef="U002">80796000</us-gaap:NetCashProvidedByUsedInFinancingActivities>
    <us-gaap:NetCashProvidedByUsedInFinancingActivities
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_af5d9d765265424f939925e68f5a2822"
      unitRef="U002">466219000</us-gaap:NetCashProvidedByUsedInFinancingActivities>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_d3528cb59540483eab0bc9587f782713"
      unitRef="U002">-30881000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_6c7116234ecd426ba14d70e6a235d6d3"
      unitRef="U002">350261000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20181231"
      decimals="-3"
      id="Fact_fd5df9e35af74f35a9bce6f143774041"
      unitRef="U002">278820000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20171231"
      decimals="-3"
      id="Fact_23118be8b83a46f58f22e69cb8f9077f"
      unitRef="U002">129630000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20190930"
      decimals="-3"
      id="Fact_501d02ebc89a4528bbf4865fc32ff7e1"
      unitRef="U002">247939000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20180930"
      decimals="-3"
      id="Fact_ca87839d08a24d358e12b10cb090aa04"
      unitRef="U002">479891000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:InterestPaidNet
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_9c49e11cb9ce4f04aa4b433d927debc7"
      unitRef="U002">5474000</us-gaap:InterestPaidNet>
    <us-gaap:InterestPaidNet
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_fa5b8cf53b3c4bf1895fa0b855713236"
      unitRef="U002">5434000</us-gaap:InterestPaidNet>
    <us-gaap:IncomeTaxesPaid
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_7cebb5b6555248abbae68e2f9f007feb"
      unitRef="U002">9037000</us-gaap:IncomeTaxesPaid>
    <us-gaap:IncomeTaxesPaid
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_aefef64320704192be3ed39022abf12f"
      unitRef="U002">0</us-gaap:IncomeTaxesPaid>
    <us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_e6053bdbbbff4c51841678e272ea95e7"
      unitRef="U002">14178000</us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability>
    <us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_d8be1f56d6d14b7d84ffa49e06d25230"
      unitRef="U002">0</us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability>
    <ions:NonCashCapitalAndPatentExpenditures
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_dacc7af35ad249f79558b3fe83347b6a"
      unitRef="U002">3251000</ions:NonCashCapitalAndPatentExpenditures>
    <ions:NonCashCapitalAndPatentExpenditures
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_85c1067a8a3d410db856b7d9c92b35c6"
      unitRef="U002">2296000</ions:NonCashCapitalAndPatentExpenditures>
    <us-gaap:CapitalExpendituresIncurredButNotYetPaid
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_1dd1fdaf707e40b694575f1bfaa77147"
      unitRef="U002">0</us-gaap:CapitalExpendituresIncurredButNotYetPaid>
    <us-gaap:CapitalExpendituresIncurredButNotYetPaid
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_9ae6012fd0b94c25a1d0a9e5f51de08d"
      unitRef="U002">3596000</us-gaap:CapitalExpendituresIncurredButNotYetPaid>
    <us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock
      contextRef="c20190101to20190930"
      id="Text_b498b17d23e34d2589e5773394842304">
&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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended&#160;September 30, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. &lt;/span&gt;In July 2017, Akcea completed an &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;initial public offering, or IPO,&lt;/span&gt; and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx.&lt;/sub&gt;. At September 30, 2019, our ownership was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#x2019;s license of AKCEA-ANGPTL3-L&lt;sub&gt;Rx&lt;/sub&gt;. We reflect changes in our ownership of Akcea in our financial statements in the period the change occurs. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Refer to the section titled &#x201c;Noncontrolling Interest in Akcea&#x201d; in Note 2, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies,&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for further information related to our accounting for our investment in Akcea.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unless the context requires otherwise, &#x201c;Ionis&#x201d;, &#x201c;Company,&#x201d; &#x201c;we,&#x201d; &#x201c;our,&#x201d; and &#x201c;us&#x201d; refers to Ionis Pharmaceuticals, Inc. and its majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries.&lt;/div&gt;
</us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock>
    <us-gaap:BasisOfAccountingPolicyPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_905a4e511c60423b989b43e99337abf6">
&lt;div style="display:none;"&gt;&lt;br/&gt;&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 and nine months ended&#160;September 30, 2019 and 2018 on the same basis as the audited financial statements for the year ended December 31, 2018. 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. Results for the interim periods are not necessarily indicative of the results 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, 2018 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="c20190101to20190930"
      id="Text_c4fe943e7ede4d098552ec8bdd246050">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries. We formed Akcea in December 2014. &lt;/span&gt;In July 2017, Akcea completed an &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;initial public offering, or IPO,&lt;/span&gt; and therefore, beginning in July 2017, we no longer owned 100 percent of Akcea. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx.&lt;/sub&gt;. At September 30, 2019, our ownership was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#x2019;s license of AKCEA-ANGPTL3-L&lt;sub&gt;Rx&lt;/sub&gt;. We reflect changes in our ownership of Akcea in our financial statements in the period the change occurs. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Refer to the section titled &#x201c;Noncontrolling Interest in Akcea&#x201d; in Note 2, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies,&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for further information related to our accounting for our investment in Akcea.&lt;/span&gt;&lt;/div&gt;
</us-gaap:ConsolidationPolicyTextBlock>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_5363570e60de48029520ca50e5d8bcc6"
      unitRef="U003">1</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <ions:ReceiptOfSharesInSubsidiary
      contextRef="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="-5"
      id="Fact_7d73810a223b46b69a6b2753b0deaba8"
      unitRef="U001">2800000</ions:ReceiptOfSharesInSubsidiary>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_41aca5c969014ccb8a724b491c9c534a"
      unitRef="U003">0.75</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <ions:ReceiptOfSharesInSubsidiary
      contextRef="c20191001to20191231_OwnershipAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember"
      decimals="-5"
      id="Fact_8ae685fa3c5b421b95d53e7fe1b68c91"
      unitRef="U001">6900000</ions:ReceiptOfSharesInSubsidiary>
    <us-gaap:SignificantAccountingPoliciesTextBlock
      contextRef="c20190101to20190930"
      id="Text_e79356058bb74d2aa7d3df4a10cdfef1">
&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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue Recognition&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: Product sales, net&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. &lt;/span&gt;In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Europe, prior to the third quarter of 2019 we distributed TEGSEDI through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL was our sole customer in Europe. The 3PL in Europe then distributed TEGSEDI to hospitals and pharmacies. In the third quarter of 2019, we entered into a distribution arrangement with a 3PL and began to sell both TEGSEDI and WAYLIVRA directly to hospitals and pharmacies in Europe.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We provide details about our collaboration agreements in Note 7, &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; in our Annual Report on Form 10-K for the year ended December 31, 2018&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;.&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za828ef045c5342ec950720727f58194e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z423ff748c87641c8b173de2f4fc02db9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf1c5606cc4d545ceaeee39b9216b6706" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have identified our rights, our partner&#x2019;s rights and the payment terms;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd1b38b04c6d44ee2a317b490bdd9a611" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zdc1a47e8a7f84ce9b17a88c78aaa2813" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 is probable. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z154b7c49dc104a57ab977ae0e4e30809" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;2.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Often times 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. These items are contingent upon future events that may not occur. 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0c7f5c3635d344b3a58160ef8667cdcd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when Roche dosed the first patient in the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx &lt;/sub&gt;(RG6042). We did not consider these milestone payments probable until Roche achieved the milestone event because the dosing of a patient was a contingent event that was not within our control. We recognized the milestone payments in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payments.&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6b0a5e16e14f413e9cb3790671d564a2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;4.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Allocate the transaction price&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1050d76f512c44499a8a4a55c6cd90ec" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc0968e72382e45d9a26ab5eae98b5ed7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 on future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zdc34827c6d5d41dabfa0b3a3713d80db" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;Contractual milestone payments;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc92b502b421a42638f6c4797795c4af4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expenses we expect to incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc9eaca6cecc84fc5a8f56282da85c4c1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;Income taxes; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9f345c6a9ccf4de79419b350e5a3fc46" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7a4859a1235b498a8927bb7e99a59f30" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The number of internal hours we estimate we will spend performing these services;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z479e033d5771475ab32e613cf9bf9239" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work we will perform;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z781255f68a404a85aa0ec8ffb0f8d24f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6ce136f034fc4177890b3f2eae4d4f3a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb5abc673cc6d48aa89e5180f190cfad5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -54pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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. For example, &lt;/span&gt;in the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation under our&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 2013 Strategic Neurology collaboration with Biogen&lt;/span&gt;. As of September 30, 2019, we have completed a&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; significant portion of the research and development services. We expect to complete the remainder of our services in 2020. As a result of our change in estimate, in the third quarter of 2019, we recorded a cumulative catch up adjustment of $&lt;/span&gt;16.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to decrease revenue. We expect to complete the remainder of our services in 2020. Refer to Note 7, &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 further discussion of the cumulative catch up adjustment we made.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/span&gt;&lt;/span&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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: Product sales, net&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize product sales in the period &lt;/span&gt;when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities.&lt;/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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period.&lt;/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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are the components of variable consideration related to product sales:&lt;/div&gt;

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

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Chargebacks: &lt;/span&gt;In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record reserves for these chargebacks related to product sales to our U.S. customer during the reporting period.&lt;/div&gt;

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

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Government rebates&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;: We are subject t&lt;/span&gt;o discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Trade discounts: &lt;/span&gt;We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Distribution services&lt;/span&gt;: We receive and pay for various distribution services from our U.S. and EU customers and wholesalers in the U.S. For services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value, we classify the costs for such services as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as selling, general and administration, or SG&amp;amp;A, expenses.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Product returns: &lt;/span&gt;Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#x2019;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we believe we will have minimal returns. Our EU customers only take title to the product after they receive an order from a hospital or pharmacy and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in the EU and we do not estimate returns in the EU.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Other incentives: &lt;/span&gt;In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Research and development revenue under collaboration agreements:&lt;/span&gt;&lt;/span&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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. For example, under our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;collaboration agreement with Roche to&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases&lt;/span&gt;, 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced a new target for an unidentified neurological disease under our 2018 strategic neurology 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2019, we recognized an $8 million milestone payment &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;when Biogen initiated a Phase 1/2 study of IONIS-LRRK2&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (BIIB094) for the treatment of people with Parkinson&#x2019;s disease&lt;/span&gt;. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We concluded that the milestone payment was not related to our R&amp;amp;D services performance obligation. Therefore, we recognized the milestone payment in full in the third quarter of 2019.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. &lt;/span&gt;For example, in the third quarter of 2019, we earned a $25 million license fee when GSK licensed our HBV program from us.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. &lt;/span&gt;For example, in the second quarter of 2019, we earned a $20 million sublicense fee when Alnylam Pharmaceuticals sublicensed our technology to Regeneron Pharmaceuticals.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd501d31562294c6aaa719422cd15d756" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3dd236033f64fc69c60fe14eb86f927" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are at a stand-alone selling price. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 at their 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the prevention of thrombosis. As part of the agreement, Bayer paid us a $&lt;/span&gt;100&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and to initiate development of IONIS-FXI-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-FXI-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Under the 2017 amendment, we concluded we had a new agreement with &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, to provide R&amp;amp;D services and to deliver API. We allocated the $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million transaction price to these performance obligations. &lt;/span&gt;Refer to &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 7, &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;, for further discussion &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;of our accounting treatment for our Bayer collaboration.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z647b2221962b4885b6203f5375ade9eb" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24d42ec8f51f41848c8f9d33210e47e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf3b846712a0f4085b6899ba8ff04e10d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 September 30, 2019 and 2018, we recognized $30.3 million and $37.2 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the nine months ended&#160;September 30, 2019 and 2018, we recognized $103.5 million and $80.4 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Products Sold&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed a significant portion of the costs we incurred to produce the supply for each medicine we are using in the commercial launch as research and development expense. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We previously expensed $&lt;/span&gt;0.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;0.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of costs to produce our products related to the product sales revenue we recognized in the&lt;/span&gt;&#160;three and nine months ended September 30, 2019, respectively.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to Akcea&#x2019;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#x2019;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#x2019;s stock related to our license of TEGSEDI and AKCEA-TTR-L&lt;sub&gt;Rx&lt;/sub&gt; to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, increasing our ownership to approximately 76 percent at March 31, 2019. At September 30, 2019, our ownership in Akcea was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#x2019;s license of AKCEA-ANGPTL3-L&lt;sub&gt;Rx&lt;/sub&gt;. We reflect changes in our ownership of Akcea in our financial statements as an adjustment to noncontrolling interest in the period the change occurs. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The shares third parties own represent an interest in Akcea&#x2019;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock in a separate line on the statement of operations and a separate line within stockholders&#x2019; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#x2019; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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. We use the specific identification method to determine the cost of securities sold.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 September 30, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market 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. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We obtained the first regulatory approval for TEGSEDI in July 2018 and in May 2019 for WAYLIVRA. At September 30, 2019, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;amp;D expenses.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did &lt;/span&gt;no&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;t record any material inventory write-offs for the &lt;/span&gt;nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Total inventory was $&lt;/span&gt;19.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;8.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million as of &lt;/span&gt;September 30, 2019 and December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, respectively.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Topic 842 Adoption&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In February 2016, the Financial Accounting Standards Board, or FASB, issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/span&gt;, or Topic 840, and created a new lease accounting standard, Topic 842, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/span&gt;, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing lease, it will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. &lt;/span&gt;The adoption did not have an impact on our condensed consolidated statement of operations.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Leases&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;We determined the lease term at the inception of the 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.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#x2019;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 or as of the lease inception date in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&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;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&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 United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#x2019;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Income (Loss) Per Share&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net income (loss) per share&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.&lt;/div&gt;

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,221&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.34&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,772&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,772&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2019, was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,174&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,174&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,538&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.73&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,346&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.03&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2018, was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,347&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.93&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,517&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43,163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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;Dilutive net income (loss per share)&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&lt;span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the three months ended September 30, 2019&lt;/span&gt;&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&lt;span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt; as follows (in thousands except per share amounts):&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;0.19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;844&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our Employee Stock Purchase Plan&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,408&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the nine months ended&#160;September 30, 2019 as follows (in thousands except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;0.81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,208&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;793&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our Employee Stock Purchase Plan&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;142,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.79&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended September 30, 2018, 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5651e0539b1741fda1231d28f3d75c17" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7e90304a08cb4b28bbe2c90004d5b48d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options; &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z503eee239a9647d2b0c553764a10ff4d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7ddd358f5ffd49cb80e76497ec47f5cc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment Information&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is &lt;/span&gt;a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#x2019; development, R&amp;amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-based Compensation Expense&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#160;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;60.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63.1&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; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;60.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;45.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis RSU&#x2019;s:&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year period. The weighted-average grant date fair value of RSUs granted to employees for the nine months ended&#160;September 30, 2019 was $59.79 per share. The weighted-average grant date fair value of RSUs granted to our board of directors for the nine months ended&#160;September 30, 2019 was $64.65 per share.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In addition to our stock plans, Akcea has its own stock plan under which it grants stock options and RSUs and under which it derives its stock-based compensation expense. &lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&#160;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;September 30, 2019&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt; and 2018&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;: &lt;/span&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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.7&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;75.6&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;77.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;73.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.4 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;"&gt;Akcea ESPP:&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands).&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/&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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;Cost of products sold&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,744&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,780&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;255&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,103&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,246&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total non-cash stock-based compensation expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,126&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111,564&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;97,210&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the third quarter of 2019, three Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $19.1 million of stock-based compensation expense it had previously recognized related to the executive officers&#x2019; stock options and RSUs that were no longer going to vest.&lt;/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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $143.9 million and $71.3 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 non-vested stock options and RSUs over a weighted average amortization period of 1.2 years and 1.6 years, respectively.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan to increase the total number of shares reserved for issuance under the plan from 16 million to 23 million shares.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2019, our board of directors approved an initial share repurchase program of up to $125 million of our common stock. Our stock repurchase program has no expiration date. To date, we have not repurchased any shares of our common stock.&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. We plan to adopt this guidance on January 1, 2020 on a prospective basis. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8bdd29a294eb40de9936181c921e770a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcfd41a05fd534170aa5bf96451b5d895" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z01a3ba1f007c4a6aa41b051b55d3c310" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adds &#x201c;unit of account&#x201d; concept to collaboration accounting guidance to align with Topic 606. The &#x201c;unit of account&#x201d; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf0bc1b58e5944c7c95ca172b59ca15bd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;We will use the &#x201c;unit of account&#x201d; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8b99d6ac86964c488e342898b48a042f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z991322bb7f8b47b487f7e37acfd889f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it could have on our condensed consolidated financial statements and disclosures.&lt;/div&gt;
</us-gaap:SignificantAccountingPoliciesTextBlock>
    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_a7941b74efeb4884837e75cd6f25191b">
&lt;div style="display:none;"&gt;&lt;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="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue Recognition&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue future sales milestone payments and royalties we earn under our partnerships.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: Product sales, net&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. &lt;/span&gt;In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Europe, prior to the third quarter of 2019 we distributed TEGSEDI through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL was our sole customer in Europe. The 3PL in Europe then distributed TEGSEDI to hospitals and pharmacies. In the third quarter of 2019, we entered into a distribution arrangement with a 3PL and began to sell both TEGSEDI and WAYLIVRA directly to hospitals and pharmacies in Europe.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We provide details about our collaboration agreements in Note 7, &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; in our Annual Report on Form 10-K for the year ended December 31, 2018&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;.&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za828ef045c5342ec950720727f58194e" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z423ff748c87641c8b173de2f4fc02db9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf1c5606cc4d545ceaeee39b9216b6706" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have identified our rights, our partner&#x2019;s rights and the payment terms;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd1b38b04c6d44ee2a317b490bdd9a611" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zdc1a47e8a7f84ce9b17a88c78aaa2813" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 is probable. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z154b7c49dc104a57ab977ae0e4e30809" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;2.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Often times 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. These items are contingent upon future events that may not occur. 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0c7f5c3635d344b3a58160ef8667cdcd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when Roche dosed the first patient in the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx &lt;/sub&gt;(RG6042). We did not consider these milestone payments probable until Roche achieved the milestone event because the dosing of a patient was a contingent event that was not within our control. We recognized the milestone payments in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payments.&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6b0a5e16e14f413e9cb3790671d564a2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;4.&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Allocate the transaction price&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1050d76f512c44499a8a4a55c6cd90ec" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc0968e72382e45d9a26ab5eae98b5ed7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 on future product sales;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zdc34827c6d5d41dabfa0b3a3713d80db" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;Contractual milestone payments;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc92b502b421a42638f6c4797795c4af4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expenses we expect to incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc9eaca6cecc84fc5a8f56282da85c4c1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;Income taxes; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9f345c6a9ccf4de79419b350e5a3fc46" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7a4859a1235b498a8927bb7e99a59f30" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The number of internal hours we estimate we will spend performing these services;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z479e033d5771475ab32e613cf9bf9239" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work we will perform;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z781255f68a404a85aa0ec8ffb0f8d24f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6ce136f034fc4177890b3f2eae4d4f3a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb5abc673cc6d48aa89e5180f190cfad5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -54pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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. For example, &lt;/span&gt;in the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation under our&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 2013 Strategic Neurology collaboration with Biogen&lt;/span&gt;. As of September 30, 2019, we have completed a&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; significant portion of the research and development services. We expect to complete the remainder of our services in 2020. As a result of our change in estimate, in the third quarter of 2019, we recorded a cumulative catch up adjustment of $&lt;/span&gt;16.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to decrease revenue. We expect to complete the remainder of our services in 2020. Refer to Note 7, &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 further discussion of the cumulative catch up adjustment we made.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are examples of when we typically recognize revenue based on the types of payments we receive.&lt;/div&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/span&gt;&lt;/span&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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Commercial Revenue: Product sales, net&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize product sales in the period &lt;/span&gt;when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities.&lt;/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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period.&lt;/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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are the components of variable consideration related to product sales:&lt;/div&gt;

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

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Chargebacks: &lt;/span&gt;In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record reserves for these chargebacks related to product sales to our U.S. customer during the reporting period.&lt;/div&gt;

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

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Government rebates&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;: We are subject t&lt;/span&gt;o discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Trade discounts: &lt;/span&gt;We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Distribution services&lt;/span&gt;: We receive and pay for various distribution services from our U.S. and EU customers and wholesalers in the U.S. For services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value, we classify the costs for such services as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as selling, general and administration, or SG&amp;amp;A, expenses.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Product returns: &lt;/span&gt;Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#x2019;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we believe we will have minimal returns. Our EU customers only take title to the product after they receive an order from a hospital or pharmacy and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in the EU and we do not estimate returns in the EU.&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Other incentives: &lt;/span&gt;In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Research and development revenue under collaboration agreements:&lt;/span&gt;&lt;/span&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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. For example, under our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;collaboration agreement with Roche to&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases&lt;/span&gt;, 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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced a new target for an unidentified neurological disease under our 2018 strategic neurology 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2019, we recognized an $8 million milestone payment &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;when Biogen initiated a Phase 1/2 study of IONIS-LRRK2&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (BIIB094) for the treatment of people with Parkinson&#x2019;s disease&lt;/span&gt;. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We concluded that the milestone payment was not related to our R&amp;amp;D services performance obligation. Therefore, we recognized the milestone payment in full in the third quarter of 2019.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. &lt;/span&gt;For example, in the third quarter of 2019, we earned a $25 million license fee when GSK licensed our HBV program from us.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. &lt;/span&gt;For example, in the second quarter of 2019, we earned a $20 million sublicense fee when Alnylam Pharmaceuticals sublicensed our technology to Regeneron Pharmaceuticals.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd501d31562294c6aaa719422cd15d756" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3dd236033f64fc69c60fe14eb86f927" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are at a stand-alone selling price. &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 at their 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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the prevention of thrombosis. As part of the agreement, Bayer paid us a $&lt;/span&gt;100&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and to initiate development of IONIS-FXI-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and IONIS-FXI-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Under the 2017 amendment, we concluded we had a new agreement with &lt;/span&gt;three&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, to provide R&amp;amp;D services and to deliver API. We allocated the $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million transaction price to these performance obligations. &lt;/span&gt;Refer to &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 7, &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;, for further discussion &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;of our accounting treatment for our Bayer collaboration.&lt;/span&gt;&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z647b2221962b4885b6203f5375ade9eb" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24d42ec8f51f41848c8f9d33210e47e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf3b846712a0f4085b6899ba8ff04e10d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;
</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
    <ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract
      contextRef="c20190101to20190930"
      decimals="INF"
      id="Fact_a5d99bad3ce4453ea2bcc34d06e92ad6"
      unitRef="U005">1</ions:RevenueFromContractWithCustomerNumberOfPerformanceObligationsAtInceptionOfContract>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"
      decimals="-6"
      id="Fact_df927636533f42d0b09abafe0eac07cb"
      unitRef="U002">35000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"
      decimals="-5"
      id="Fact_517d03b46cca46a9b5decb28e94b3566"
      unitRef="U002">-16500000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:UpfrontPaymentReceived
      contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember"
      decimals="-6"
      id="Fact_72588160d9344e3d91319fe6a66f7d24"
      unitRef="U002">75000000</ions:UpfrontPaymentReceived>
    <ions:UpfrontPaymentReceived
      contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember"
      decimals="-6"
      id="Fact_df2e1cb511f24d2a84b6cc2d7d4dc617"
      unitRef="U002">75000000</ions:UpfrontPaymentReceived>
    <ions:RevenueFromContractWithCustomerTransactionPriceAdditions
      contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="-5"
      id="Fact_b1ad7b69ba7b4f49953ac99ff42d86a8"
      unitRef="U002">7500000</ions:RevenueFromContractWithCustomerTransactionPriceAdditions>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"
      decimals="-6"
      id="Fact_f61ab49d136d4efaa1f8b5c47333b449"
      unitRef="U002">8000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_0fdd42612222445c956a5927b56c7f0a"
      unitRef="U002">25000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190401to20190630_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2004WithAlnylamPharmaceuticalsIncMember"
      decimals="-6"
      id="Fact_6d686017b9d34c37a02641c0ee3ef4a8"
      unitRef="U002">20000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:UpfrontPaymentReceived
      contextRef="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"
      decimals="-6"
      id="Fact_04925e882d334a389a69c532092cf64b"
      unitRef="U002">100000000</ions:UpfrontPaymentReceived>
    <ions:UpfrontPaymentReceived
      contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember"
      decimals="-6"
      id="Fact_57a16aea2a5f41568fe5664de44e803a"
      unitRef="U002">75000000</ions:UpfrontPaymentReceived>
    <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations
      contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBayerMember"
      decimals="INF"
      id="Fact_a00b0ca9a01345a49798907658fe58a8"
      unitRef="U005">3</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember"
      decimals="-6"
      id="Fact_4db48f7dfeaa406aaa9d238c6b557cc8"
      unitRef="U002">75000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:NumberOfAgreementsWithCollaborationPartner
      contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember"
      decimals="INF"
      id="Fact_951a4e44e5184443bbbc525be5d8d3fb"
      unitRef="U006">2</ions:NumberOfAgreementsWithCollaborationPartner>
    <us-gaap:ReceivablesPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_c3bb5773b7744d1d8c746f80fd7e591e">
&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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;
</us-gaap:ReceivablesPolicyTextBlock>
    <us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy
      contextRef="c20190101to20190930"
      id="Text_069517b639814bcfb63f346d7630c6ac">
&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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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="c20190101to20190930"
      id="Text_39e2f330f3084a75956000480f2ecc99">
&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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 September 30, 2019 and 2018, we recognized $30.3 million and $37.2 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the nine months ended&#160;September 30, 2019 and 2018, we recognized $103.5 million and $80.4 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="c20190701to20190930"
      decimals="-5"
      id="Fact_29a96e3cb4bb4440a9a1b2cd97733561"
      unitRef="U002">30300000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20180701to20180930"
      decimals="-5"
      id="Fact_73cbcf1185e94594bcdf73d446b1e5e5"
      unitRef="U002">37200000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20190101to20190930"
      decimals="-5"
      id="Fact_a85dd4d0434f48769d4fff65100bcda5"
      unitRef="U002">103500000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20180101to20180930"
      decimals="-5"
      id="Fact_2a8b360fd3ed495c9f969e160446bfc8"
      unitRef="U002">80400000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_9511d33e757a42678615f83b5df904ed">
&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 Products Sold&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed a significant portion of the costs we incurred to produce the supply for each medicine we are using in the commercial launch as research and development expense. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We previously expensed $&lt;/span&gt;0.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;0.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of costs to produce our products related to the product sales revenue we recognized in the&lt;/span&gt;&#160;three and nine months ended September 30, 2019, respectively.&lt;/div&gt;
</us-gaap:CostOfSalesPolicyTextBlock>
    <ions:CostOfProductsSoldPreviouslyRecognized
      contextRef="c20190701to20190930"
      decimals="-5"
      id="Fact_629c487159874d51b46161e6540c21bc"
      unitRef="U002">200000</ions:CostOfProductsSoldPreviouslyRecognized>
    <ions:CostOfProductsSoldPreviouslyRecognized
      contextRef="c20190101to20190930"
      decimals="-5"
      id="Fact_f48bb0935b8d4e11b248cc586569cce9"
      unitRef="U002">500000</ions:CostOfProductsSoldPreviouslyRecognized>
    <us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy
      contextRef="c20190101to20190930"
      id="Text_ece58b8638f04f80b592393388f33955">
&lt;div style="display:none;"&gt;&lt;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;Noncontrolling Interest in Akcea Therapeutics, Inc.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to Akcea&#x2019;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#x2019;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#x2019;s stock related to our license of TEGSEDI and AKCEA-TTR-L&lt;sub&gt;Rx&lt;/sub&gt; to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, increasing our ownership to approximately 76 percent at March 31, 2019. At September 30, 2019, our ownership in Akcea was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#x2019;s license of AKCEA-ANGPTL3-L&lt;sub&gt;Rx&lt;/sub&gt;. We reflect changes in our ownership of Akcea in our financial statements as an adjustment to noncontrolling interest in the period the change occurs. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The shares third parties own represent an interest in Akcea&#x2019;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock in a separate line on the statement of operations and a separate line within stockholders&#x2019; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#x2019; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.&lt;/span&gt;&lt;/div&gt;
</us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_49ec7aa8448b4fb0b636f5c2fe809db9"
      unitRef="U003">1</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20170731_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_81e8ac19a87e4559825f24f967199b25"
      unitRef="U003">0.68</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20180430_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_b04aa9a84ce140dca193528dabe7b2cb"
      unitRef="U003">0.68</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20181231_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_e1b36786245e4275887232820b2e06fe"
      unitRef="U003">0.75</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <ions:ReceiptOfSharesInSubsidiary
      contextRef="c20190101to20190331_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="-5"
      id="Fact_8b20e19d078640888d7f1ed4020bb7f3"
      unitRef="U001">2800000</ions:ReceiptOfSharesInSubsidiary>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20190331_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_f1e0676599514d149a1144c81232642a"
      unitRef="U003">0.76</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_7c3a0c41d54d4122873d416c91a6bbe6"
      unitRef="U003">0.75</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <ions:ReceiptOfSharesInSubsidiary
      contextRef="c20191001to20191231_OwnershipAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember"
      decimals="-5"
      id="Fact_d912ac6eeb764ab5a965714886e7f654"
      unitRef="U001">6900000</ions:ReceiptOfSharesInSubsidiary>
    <ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_cac3a0042b7c4b1fba021dd7fa0e0a6f">
&lt;div style="display:none;"&gt;&lt;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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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. We use the specific identification method to determine the cost of securities sold.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 September 30, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.&lt;/div&gt;
</ions:CashCashEquivalentsAndInvestmentsPolicyTextBlock>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20190930"
      decimals="INF"
      id="Fact_8037e90f29fb43ae9797ff009a688387"
      unitRef="U007">2</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20190930"
      decimals="INF"
      id="Fact_42a31c163e8a40a8894a3145e0b1c651"
      unitRef="U007">4</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_31e43aa1cfc849aebac03eff56f0c301">
&lt;div style="display:none;"&gt;&lt;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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market 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. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We obtained the first regulatory approval for TEGSEDI in July 2018 and in May 2019 for WAYLIVRA. At September 30, 2019, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;amp;D expenses.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did &lt;/span&gt;no&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;t record any material inventory write-offs for the &lt;/span&gt;nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Total inventory was $&lt;/span&gt;19.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;8.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million as of &lt;/span&gt;September 30, 2019 and December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, respectively.&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:InventoryWriteDown
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_f8b23610178f4edc95899a9899da8223"
      unitRef="U002">0</us-gaap:InventoryWriteDown>
    <us-gaap:InventoryNet
      contextRef="c20190930"
      decimals="-5"
      id="Fact_a25964c9ffea42bf8fc7de576a76596b"
      unitRef="U002">19400000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20181231"
      decimals="-5"
      id="Fact_44dd20165015443893e9dc2dbfa04d40"
      unitRef="U002">8600000</us-gaap:InventoryNet>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_dab9a4f4745349fcabd0a7206f8be4ec">
&lt;div style="display:none;"&gt;&lt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Topic 842 Adoption&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In February 2016, the Financial Accounting Standards Board, or FASB, issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/span&gt;, or Topic 840, and created a new lease accounting standard, Topic 842, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Leases&lt;/span&gt;, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing lease, it will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. &lt;/span&gt;The adoption did not have an impact on our condensed consolidated statement of operations.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Leases&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;We determined the lease term at the inception of the 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.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#x2019;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 or as of the lease inception date in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;
</us-gaap:LesseeLeasesPolicyTextBlock>
    <us-gaap:OperatingLeaseRightOfUseAsset
      contextRef="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member"
      decimals="-5"
      id="Fact_2e29b349bb85448f954a632df4428999"
      unitRef="U002">13500000</us-gaap:OperatingLeaseRightOfUseAsset>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member"
      decimals="-5"
      id="Fact_182b919ed3e64fc4b0825beb4f643f7a"
      unitRef="U002">18500000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseLiabilityCurrent
      contextRef="c20181231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate201602Member"
      decimals="-6"
      id="Fact_aa18508f1ac14387a7398aea8afb242c"
      unitRef="U002">2000000</us-gaap:OperatingLeaseLiabilityCurrent>
    <us-gaap:ResearchAndDevelopmentExpensePolicy
      contextRef="c20190101to20190930"
      id="Text_83efbe2afbbc4a539b023aed0fc786c9">&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&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;/span&gt;</us-gaap:ResearchAndDevelopmentExpensePolicy>
    <us-gaap:IntangibleAssetsFiniteLivedPolicy
      contextRef="c20190101to20190930"
      id="Text_1afefe4da9aa4d7b9012855eb852c721">&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&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 United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.&lt;/span&gt;</us-gaap:IntangibleAssetsFiniteLivedPolicy>
    <us-gaap:IncomeTaxPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_25282174729d4998ab5c7a9816f3daef">
&lt;div style="display:none;"&gt;&lt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 style="text-align: justify;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#x2019;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.&lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_c8392968e6a441099a970062bcd082df">
&lt;div style="display:none;"&gt;&lt;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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, 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="c20190101to20190930"
      id="Text_bd277cfebfa84a259359328ea8ed2a76">
&lt;div style="display:none;"&gt;&lt;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;Use of Estimates&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_2da7bfa9547f4a7dbb2f9930781fb07b">
&lt;div style="display:none;"&gt;&lt;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;Basic and Diluted Net Income (Loss) Per Share&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net income (loss) per share&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.&lt;/div&gt;

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,221&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.34&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,772&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,772&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2019, was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,174&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,174&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,538&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.73&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,346&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.03&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2018, was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,347&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.93&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,517&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43,163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&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;Dilutive net income (loss per share)&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.&lt;/div&gt;

&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;
&lt;span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the three months ended September 30, 2019&lt;/span&gt;&lt;span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt; as follows (in thousands except per share amounts):&lt;/span&gt;
&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;0.19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;844&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our Employee Stock Purchase Plan&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,408&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the nine months ended&#160;September 30, 2019 as follows (in thousands except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;0.81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,208&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;793&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our Employee Stock Purchase Plan&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;142,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.79&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended&#160;September 30, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three and nine months ended September 30, 2018, 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5651e0539b1741fda1231d28f3d75c17" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7e90304a08cb4b28bbe2c90004d5b48d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options; &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z503eee239a9647d2b0c553764a10ff4d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7ddd358f5ffd49cb80e76497ec47f5cc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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;
</us-gaap:EarningsPerSharePolicyTextBlock>
    <us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock
      contextRef="c20190101to20190930"
      id="Text_8d8b0369ff0848a090cf672c2c7b5324">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,221&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.34&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,772&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,772&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net income per share for the nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2019, was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.40&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,174&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,174&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,538&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.73&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(47,843&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,617&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,346&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.03&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the nine months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;September 30, 2018, was calculated as follows (in thousands, except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis&#x2019; Portion of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea&#x2019;s Net Loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Common shares&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,347&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.93&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss attributable to our ownership&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(110,680&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net income&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67,517&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43,163&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.33&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock>
    <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary
      contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_43c87bc87ac5417fbf0a113ba2c3234a"
      unitRef="U001">70221000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="2"
      id="Fact_ce3442e281e8408982b337f4368ffcf2"
      unitRef="U004">-0.34</us-gaap:EarningsPerShareBasic>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_2ec32aecd2af4dc1a8b56a25f22107df"
      unitRef="U002">-23772000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="-3"
      id="Fact_79895e95b2894e3eb06f1387172f7322"
      unitRef="U002">-23772000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190701to20190930_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_3ae9d4e6a9164c458bd06e9241ed229f"
      unitRef="U002">49930000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_57bf878287e349068e6f30c6291cbee9"
      unitRef="U002">26158000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_a141a342ad8243d89879365ffd24543f"
      unitRef="U001">140551000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190701to20190930"
      decimals="2"
      id="Fact_4c76f7f37884447aa99306b954311210"
      unitRef="U004">0.19</us-gaap:EarningsPerShareBasic>
    <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary
      contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_147163d75a3b4ff496d72c16efd9604d"
      unitRef="U001">69681000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="2"
      id="Fact_e8d0fd372c814f06a8e5e97032b606c0"
      unitRef="U004">-0.40</us-gaap:EarningsPerShareBasic>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_bf9ab4c5a403467d998d19366486515d"
      unitRef="U002">-28174000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="-3"
      id="Fact_1b364a5b33474bc8b9b91b217972d565"
      unitRef="U002">-28174000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20190101to20190930_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_28ac53378e8446b29b2685ada729d8c7"
      unitRef="U002">140938000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_db3be26cc6a246d496d524251c4de3dd"
      unitRef="U002">112764000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_ddea2641661a48a19609e7b6ab683674"
      unitRef="U001">139800000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190101to20190930"
      decimals="2"
      id="Fact_d6aa6f0722e04f51922eb5ba015c6a45"
      unitRef="U004">0.81</us-gaap:EarningsPerShareBasic>
    <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary
      contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_35767e855cbf450cb21d26c324a1d927"
      unitRef="U001">65538000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="2"
      id="Fact_5e959d88aa6c46ca89a333d0d6cd3637"
      unitRef="U004">-0.73</us-gaap:EarningsPerShareBasic>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_b5a98a2a39f941be9021fd6378d498c6"
      unitRef="U002">-47843000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="-3"
      id="Fact_b3c04982056e46bb89fc30c57b93d79c"
      unitRef="U002">-47843000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180701to20180930_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_0942c549bec2404c85d6c5d2d875dbfb"
      unitRef="U002">43226000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_12b944156d8e4b299dabc78291bbcf94"
      unitRef="U002">-4617000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_3690cd8d6cdf42c2b5de20022a93ff4c"
      unitRef="U001">137346000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20180701to20180930"
      decimals="2"
      id="Fact_1dcf9ad2d573436e802c08844b4a926e"
      unitRef="U004">-0.03</us-gaap:EarningsPerShareBasic>
    <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary
      contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_ac3dd463ed9d4bf9862f1f070652c598"
      unitRef="U001">57347000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="2"
      id="Fact_69fbad8094384f33bc9707e3f6adbf24"
      unitRef="U004">-1.93</us-gaap:EarningsPerShareBasic>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember"
      decimals="-3"
      id="Fact_8650f31a880a4b12a608b1ceb7631a4c"
      unitRef="U002">-110680000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="-3"
      id="Fact_ae8e54757cd64b5b8d2cb242050b7e43"
      unitRef="U002">-110680000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20180101to20180930_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_fe81f96af8d64d43aa22c9e8898d3879"
      unitRef="U002">67517000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_7fc30ef6106c4f99b6f1d86ceb042c8b"
      unitRef="U002">-43163000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_6c28a82b0628460eb97a165705793181"
      unitRef="U001">130507000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20180101to20180930"
      decimals="2"
      id="Fact_d812881305f747cb8ebb3e5bc9b3e57f"
      unitRef="U004">-0.33</us-gaap:EarningsPerShareBasic>
    <us-gaap:ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_74b35ce2b59647fbbe22a05f5ef21ec6">&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&lt;span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the three months ended September 30, 2019&lt;/span&gt;&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&lt;span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt; as follows (in thousands except per share amounts):&lt;/span&gt;&lt;/span&gt;
&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;0.19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;844&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our Employee Stock Purchase Plan&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,158&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143,408&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our diluted net income per share for the nine months ended&#160;September 30, 2019 as follows (in thousands except per share amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine months ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,800&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;0.81&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,208&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;793&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our Employee Stock Purchase Plan&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;142,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.79&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfEarningsPerShareBasicAndDilutedTableTextBlock>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_9fb5723a10994e27a024f7c1e5cd0716"
      unitRef="U002">26158000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_050e301828d444f3a5653ffd4c563400"
      unitRef="U001">140551000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190701to20190930"
      decimals="2"
      id="Fact_e8659768686445659dab6e86383833c8"
      unitRef="U004">0.19</us-gaap:EarningsPerShareBasic>
    <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements
      contextRef="c20190701to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="-3"
      id="Fact_43f1a62c9c264928a56d300f48e9d197"
      unitRef="U001">1993000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
    <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements
      contextRef="c20190701to20190930_AwardTypeAxis_RestrictedStockMember"
      decimals="-3"
      id="Fact_199c6529dde241af91e14231e1d53b18"
      unitRef="U001">844000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
    <ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_e649c4d03de64d178fe31f34b49bc3cd"
      unitRef="U001">20000</ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_1a9febfa42664cc3a5b9c2e21b6dffbd"
      unitRef="U002">26158000</us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_3c93baead1be4b60adcd866c0a05f9e6"
      unitRef="U001">143408000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20190701to20190930"
      decimals="2"
      id="Fact_90a490606f0b45dfae46401cba62173e"
      unitRef="U004">0.18</us-gaap:EarningsPerShareDiluted>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_6fbcb5c09e544300851e1b9a1c201df1"
      unitRef="U002">112764000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_f32580286e3a408f963e4ee172e8de31"
      unitRef="U001">139800000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20190101to20190930"
      decimals="2"
      id="Fact_0274cd0035584f309cc5af4c1934a38c"
      unitRef="U004">0.81</us-gaap:EarningsPerShareBasic>
    <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="-3"
      id="Fact_233e1fc3bc224a46bb0c8d1ffec44a84"
      unitRef="U001">2208000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
    <us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements
      contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockMember"
      decimals="-3"
      id="Fact_b7b8c402d3364c1c852cbc2b08a43732"
      unitRef="U001">793000</us-gaap:IncrementalCommonSharesAttributableToShareBasedPaymentArrangements>
    <ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_7db7a12930ae4f64978bc31beb1673b8"
      unitRef="U001">20000</ions:IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_c28e7de8515649e59a0392ea18d9cc55"
      unitRef="U002">112764000</us-gaap:NetIncomeLossAvailableToCommonStockholdersDiluted>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_2c961138725b4e11b0f070578b4446ec"
      unitRef="U001">142821000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20190101to20190930"
      decimals="2"
      id="Fact_d1af7642908b452fa7338a4148c5322d"
      unitRef="U004">0.79</us-gaap:EarningsPerShareDiluted>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_0328fad2a1ce4c8295b664c2611452cf"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20180930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_5275256bfe3946a98fa9bdf2b057c890"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_1b20b2d07f9247689a3647cff0f43791">
&lt;div style="display:none;"&gt;&lt;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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.&lt;/div&gt;
</us-gaap:DebtPolicyTextBlock>
    <us-gaap:SegmentReportingPolicyPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_97000bfae13e42c39cc8a855b0475323">
&lt;div style="display:none;"&gt;&lt;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;Segment Information&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is &lt;/span&gt;a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#x2019; development, R&amp;amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.&lt;/span&gt;&lt;/div&gt;
</us-gaap:SegmentReportingPolicyPolicyTextBlock>
    <us-gaap:NumberOfOperatingSegments
      contextRef="c20190101to20190930"
      decimals="INF"
      id="Fact_84d558a052504679b86bda59ad2a4f16"
      unitRef="U008">2</us-gaap:NumberOfOperatingSegments>
    <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy
      contextRef="c20190101to20190930"
      id="Text_ea6ca4b7f7044d6782f4b675d057249a">
&lt;div style="display:none;"&gt;&lt;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 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#160;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;60.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63.1&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; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;60.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;45.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis RSU&#x2019;s:&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year period. The weighted-average grant date fair value of RSUs granted to employees for the nine months ended&#160;September 30, 2019 was $59.79 per share. The weighted-average grant date fair value of RSUs granted to our board of directors for the nine months ended&#160;September 30, 2019 was $64.65 per share.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In addition to our stock plans, Akcea has its own stock plan under which it grants stock options and RSUs and under which it derives its stock-based compensation expense. &lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&#160;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;September 30, 2019&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt; and 2018&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;: &lt;/span&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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.7&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;75.6&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;77.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;73.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.4 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;"&gt;Akcea ESPP:&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands).&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/&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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;Cost of products sold&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,744&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,780&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;255&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,103&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,246&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total non-cash stock-based compensation expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,126&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111,564&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;97,210&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the third quarter of 2019, three Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $19.1 million of stock-based compensation expense it had previously recognized related to the executive officers&#x2019; stock options and RSUs that were no longer going to vest.&lt;/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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $143.9 million and $71.3 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 non-vested stock options and RSUs over a weighted average amortization period of 1.2 years and 1.6 years, respectively.&lt;/div&gt;
</us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy>
    <us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_64ff1eea8a674e2eac6b01877ceb01c0">
&lt;div style="text-align: left;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#160;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;60.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63.1&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; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;60.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;61.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="3"
      id="Fact_10af540d1817417c9927ac644de4ac4c"
      unitRef="U003">0.023</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="3"
      id="Fact_451b15c5e6db4150adb1ddb93a747fb2"
      unitRef="U003">0.023</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="3"
      id="Fact_297eca7f077046459d0098f137fbb6d6"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="3"
      id="Fact_59881b4df8734e98b052671b23864c88"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="3"
      id="Fact_2d88dae4193a41ada295a101a912f525"
      unitRef="U003">0.603</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="3"
      id="Fact_708d6e06317848a7a06e027a64378a15"
      unitRef="U003">0.631</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      id="Fact_2f2c71447843446799e8b051562c8b3f">P4Y7M6D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember"
      id="Fact_5a08032609f748cfba2fe024615effc1">P4Y7M6D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      decimals="3"
      id="Fact_47a2bc7c231249cb96aa9c1e7fc3ba14"
      unitRef="U003">0.019</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      decimals="3"
      id="Fact_a3b917e92a684736b97b9361a6e89260"
      unitRef="U003">0.028</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      decimals="3"
      id="Fact_74f46b234c9b4b0592f9f9845c4b3529"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      decimals="3"
      id="Fact_aa7f24671daf4a33bf1c24cc18a0d2c5"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      decimals="3"
      id="Fact_82556525924847188c081c3c2196dcf4"
      unitRef="U003">0.607</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      decimals="3"
      id="Fact_a8374861397d4239a10dc05defdd1f9b"
      unitRef="U003">0.615</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      id="Fact_eca1a2da37344e12a31ea04c3331f2ce">P6Y7M6D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember"
      id="Fact_948ea3d373ec4e10ae7d7a59d44b0757">P6Y7M6D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_e7cb432140054dd39e19ff74d588e147">
&lt;table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;45.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_775464219ddd4ea6b2ba785c16cb7f08"
      unitRef="U003">0.024</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_5b82a427bfdc485da1b5bb39d49b314f"
      unitRef="U003">0.018</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_c9bb147cbfdc4bb082d8f58b49bb33c0"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_9567f947bd664cf7a27759a728810797"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_8aec446124b44c97bbf119ee1c6f7505"
      unitRef="U003">0.456</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_ca689cbebb25416e94178e911ce5ebfa"
      unitRef="U003">0.473</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember"
      id="Fact_210f045bca1e43768566651337659487">P6M</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember"
      id="Fact_797105e5f7aa46deb02bda572ec70f0d">P6M</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1
      contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      id="Fact_0c35355dc5634225ac4bb7af9fc81af7">P4Y</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_EmployeeMember"
      decimals="2"
      id="Fact_2ed34ba20cd24f5595aac11ba305ca5e"
      unitRef="U004">59.79</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember_RelatedPartyTransactionsByRelatedPartyAxis_BoardOfDirectorsMember"
      decimals="2"
      id="Fact_7efd8b9385084843a70beff976ad9acd"
      unitRef="U004">64.65</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock
      contextRef="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Text_f70a5b3c31b0473c983800256b3d521d">&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;&#160;&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;September 30, 2019&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt; and 2018&lt;/span&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;: &lt;/span&gt;
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.7&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;75.6&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;77.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;73.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.4 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_83c4f479e627437a8ab761fa8bf3a69a"
      unitRef="U003">0.023</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_8691f84664c942b1b7b9185a59c58075"
      unitRef="U003">0.027</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_95a75a9ed6b34013be503487dd5cf87a"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_e760013ba5754d128422890beed0eece"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_3c6fea59822f4992b6a1b84e416c272e"
      unitRef="U003">0.756</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_246c29cdb32c42e6beab75d827c74d7c"
      unitRef="U003">0.771</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Fact_d5f2e36fd00242239fa02d8d861049d1">P6Y1M6D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Fact_64c1243c6d064fa9b60c00bda01677a9">P6Y1M6D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_e42a726c528e463fb0f682824f9c9d5f"
      unitRef="U003">0.018</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_d8cfdb5bb9ce4e70a764224ec0b4869c"
      unitRef="U003">0.029</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_080be06e28754a408013be5db3ecf295"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_dd82d340bf5343ed9381feb15f5f2ff5"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_e545bb0154bb4989b256872355a39745"
      unitRef="U003">0.738</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_408e3218201b47959b2c28042225c8df"
      unitRef="U003">0.782</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20190101to20190930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Fact_1fe1549d10fa427fa110919c148f3647">P6Y3M18D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20180101to20180930_AwardTypeAxis_BoardOfDirectorStockOptionMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Fact_980c44c3f9d94688835c7289ec3d5cbc">P6Y4M24D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock
      contextRef="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Text_5defb28a8f684091ae59b0adb952202f">&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;"&gt;Akcea ESPP:&lt;/span&gt;
&lt;table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;2.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_c70610c4ca26449d91c355ac8085f281"
      unitRef="U003">0.024</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_d22d8efec44a411f9761be66f7a5123c"
      unitRef="U003">0.019</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_bc12de55f91f4d44a80b4026b88edcc5"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_9985d2f174544df9b611b66bfe15d6b7"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_8598c03331034b0cb4f7ed356fa02c75"
      unitRef="U003">0.600</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="3"
      id="Fact_05881d8adb62457cb5b8270dbf6dcae0"
      unitRef="U003">0.642</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Fact_da1d41e5da0145c89e8728b8a14fd2a6">P6M</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20180101to20180930_AwardTypeAxis_EmployeeStockMember_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      id="Fact_08eb25ee394e44ee8e7f04f2ce1410fc">P6M</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock
      contextRef="c20190101to20190930"
      id="Text_7ed6498a86ce420cadfcc286dc339ff2">
&lt;div style="display:none;"&gt;&lt;br/&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 and nine months ended&#160;September 30, 2019 and 2018 (in thousands).&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/&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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td rowspan="1" 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;Cost of products sold&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,744&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,780&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;71,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;255&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,103&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,246&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total non-cash stock-based compensation expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,126&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,883&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111,564&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;97,210&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190701to20190930_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_8f8889793bc24130821266ebf7f8aedd"
      unitRef="U002">127000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180701to20180930_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_2415dad41b364b3dae6ff52d0689fc8b"
      unitRef="U002">0</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190101to20190930_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_192d34335f474b94af709bac4431ece0"
      unitRef="U002">383000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180101to20180930_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_cc18bcac872c4daf934b3a3d0edf9b5a"
      unitRef="U002">0</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190701to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_03800ecd1ad747d0aba2047e92b6de26"
      unitRef="U002">23744000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180701to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_97b3b8e52bda42f08706655a30b1f9a5"
      unitRef="U002">18780000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190101to20190930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_9367ec0b16a34e4b94468ac1f96b68d2"
      unitRef="U002">71935000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180101to20180930_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_28af0edf20b74afabc1e6a728bd3e5f1"
      unitRef="U002">57698000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190701to20190930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_4af22a8c725245f3bcdf01eb7210dd41"
      unitRef="U002">255000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180701to20180930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_70482a126d49429ead2cb0593dacedef"
      unitRef="U002">16103000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190101to20190930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_7252e6e1733947739b14991b054d4f46"
      unitRef="U002">39246000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180101to20180930_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_66d7c1fc088a447491dc7c06b11c0013"
      unitRef="U002">39512000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_df57d7e40de84153bb9ccd38c3cb39d0"
      unitRef="U002">24126000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_54690c3115b5425ab6d0ed60da8683a1"
      unitRef="U002">34883000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_cfcae472d24a41eba5315fc58eb907e1"
      unitRef="U002">111564000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_6f949baf6d1140d588b155609b49e954"
      unitRef="U002">97210000</us-gaap:AllocatedShareBasedCompensationExpense>
    <ions:NumberOfExecutiveOfficersTerminatingEmployment
      contextRef="c20190701to20190930"
      decimals="INF"
      id="Fact_3e2a0bb6aa7a475294a3bcc5865c7f50"
      unitRef="U009">3</ions:NumberOfExecutiveOfficersTerminatingEmployment>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20190701to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="-5"
      id="Fact_8beef0e24089498c95b24a2166b6b643"
      unitRef="U002">-19100000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions
      contextRef="c20190930_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="-5"
      id="Fact_6097d64058bc441eb0e524a05dd8918d"
      unitRef="U002">143900000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions
      contextRef="c20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="-5"
      id="Fact_125cca04b5d44104a490e2e882a60ceb"
      unitRef="U002">71300000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1
      contextRef="c20190101to20190930_AwardTypeAxis_EmployeeStockOptionMember"
      id="Fact_d6b9842ffb434100bea3e5d18619ca48">P1Y2M12D</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1
      contextRef="c20190101to20190930_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      id="Fact_4ff7e654f44947dc981e496d429a0f9e">P1Y7M6D</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1>
    <us-gaap:CommonStockCapitalSharesReservedForFutureIssuance
      contextRef="c20190531_PlanNameAxis_EquityIncentivePlan2011Member"
      decimals="-6"
      id="Fact_2617bf4d91164bc58917be73b8a82e6d"
      unitRef="U001">16000000</us-gaap:CommonStockCapitalSharesReservedForFutureIssuance>
    <us-gaap:CommonStockCapitalSharesReservedForFutureIssuance
      contextRef="c20190630_PlanNameAxis_EquityIncentivePlan2011Member"
      decimals="-6"
      id="Fact_1570aaadc468443bbbdf1ec8cc7cbcc3"
      unitRef="U001">23000000</us-gaap:CommonStockCapitalSharesReservedForFutureIssuance>
    <us-gaap:StockRepurchaseProgramAuthorizedAmount1
      contextRef="c20190930"
      decimals="-6"
      id="Fact_81f917a2ff44449888840b8298801f93"
      unitRef="U002">125000000</us-gaap:StockRepurchaseProgramAuthorizedAmount1>
    <us-gaap:StockRepurchasedDuringPeriodShares
      contextRef="c20190901to20190930"
      decimals="INF"
      id="Fact_3982585ef0f34f7184c70b3e49c11693"
      unitRef="U001">0</us-gaap:StockRepurchasedDuringPeriodShares>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20190101to20190930"
      id="Text_7bbc749ed0e449e5a4349828ccd31bda">
&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;Impact of Recently Issued Accounting Standards&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. We plan to adopt this guidance on January 1, 2020 on a prospective basis. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2018, the FASB issued clarifying guidance of the interaction between the collaboration accounting guidance and the new revenue recognition guidance we adopted on January 1, 2018 (Topic 606). Below is the clarifying guidance and how we will implement it (in italics):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8bdd29a294eb40de9936181c921e770a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcfd41a05fd534170aa5bf96451b5d895" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z01a3ba1f007c4a6aa41b051b55d3c310" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adds &#x201c;unit of account&#x201d; concept to collaboration accounting guidance to align with Topic 606. The &#x201c;unit of account&#x201d; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf0bc1b58e5944c7c95ca172b59ca15bd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;We will use the &#x201c;unit of account&#x201d; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8b99d6ac86964c488e342898b48a042f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z991322bb7f8b47b487f7e37acfd889f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 72pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&#x25cf;&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction &lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it could have on our condensed consolidated financial statements and disclosures.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <invest:InvestmentTextBlock
      contextRef="c20190101to20190930"
      id="Text_40768e1867ba41969846e8cd090324fe">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 0.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3.&#160; Investments&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2019, we had invested our excess cash primarily in debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#x2019;s, Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 September 30, 2019:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zcf07523367524c41877d56d489917e98" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;One year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After one year but within two years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After two years but within three years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: 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; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As illustrated above, at September 30, 2019, 91 percent of our available-for-sale securities had a maturity of less than two years.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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 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;At September 30, 2019, we had an ownership interest of less than 20 percent in four private companies and two public companies with which we conduct business. The privately-held companies are Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd. The publicly-traded companies are ProQR and ATL.&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;The following is a summary of our investments (in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zb56166283a7847d5befc091adecaa6a1" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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; font-weight: bold;"&gt;September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;752,495&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,484&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;753,831&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176,589&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176,865&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331,371&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;264&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331,618&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,986&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,963&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,297,389&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,299,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;539,820&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,108&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;106,536&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;101&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;106,500&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#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: 18pt; 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;34,692&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;(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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,654&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,283&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,302&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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;690,331&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,234&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(342&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', 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;693,223&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,987,720&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,307&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(579&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,992,448&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,988,932&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;5,307&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,993,054&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zf8befa7024ac4c7aaab0e6b0e3be21d5" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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; font-weight: bold;"&gt;December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;956,879&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,858&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;955,034&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;168,839&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(104&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;168,738&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;244,640&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(77&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;244,578&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63,572&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(323&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63,249&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,433,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,431,599&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;299,018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;194&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,286&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;297,926&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;107,789&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;194&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(109&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;107,874&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,576&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,980&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;(287&lt;/div&gt;&lt;/td&gt;
    &lt;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;16,693&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;439,387&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;388&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,706&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438,069&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,873,317&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,068&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,869,668&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current 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;1,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,874,529&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;556&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,068&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,871,017&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze2689b040009421da56fad38f1ad9a5f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our available-for-sale securities are held at amortized cost.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4c2e520a6c644d0f8f16eee8ae381f87" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z94b340357ef0469db6ab0f6c9e7f6ab9" style="font-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;We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments we consider to be temporarily impaired at September 30, 2019. 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;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z78a191fc6a1c47b5bbf4c2cc8e099df3" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" 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;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;(In thousands)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;104&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;304,705&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(268&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,675&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(41&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;336,380&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF; 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%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;102,733&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(156&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,974&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(26&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;125,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,918&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(55&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,918&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(55&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF; 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,498&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,597&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(33&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;486,854&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(480&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,246&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(99&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;557,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(579&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</invest:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_323a4af8c563455381e38fef93df2fd6">
&lt;div style="display:none;"&gt;&lt;br/&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 September 30, 2019:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zcf07523367524c41877d56d489917e98" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;One year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After one year but within two years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After two years but within three years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: 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; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20190101to20190930"
      id="Fact_4b3282e6abbf4694b90d56a12cb3a78d">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
      contextRef="c20190930"
      decimals="2"
      id="Fact_26a36804df4340729bec0b2f463acda4"
      unitRef="U003">0.69</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20190101to20190930"
      id="Fact_3bd993e525784a5398b297b7856fe228">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20190101to20190930"
      id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20190930"
      decimals="2"
      id="Fact_b3c2ee50dd694d208197df43360458a9"
      unitRef="U003">0.22</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20190101to20190930"
      id="Fact_812c571149d64b329fe4410606d76c7a">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:MaximumContractMaturityPeriodRange3
      contextRef="c20190101to20190930"
      id="Fact_f12cc57cfa544d218ac6c26f9aae5797">P3Y</ions:MaximumContractMaturityPeriodRange3>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage
      contextRef="c20190930"
      decimals="2"
      id="Fact_8cd01e7f5688446294ec6f1b2d7e38df"
      unitRef="U003">0.09</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20190930"
      decimals="2"
      id="Fact_6217a171f5784696968b178278e97ffa"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20190930"
      decimals="2"
      id="Fact_7de0397396204971870c9dfa3dc16f94"
      unitRef="U003">0.91</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20190101to20190930"
      id="Fact_34c87d75876e42c988ffebc06f56b6a3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20190930"
      decimals="INF"
      id="Fact_b7edbc55e46842cb916a4ced56279788"
      unitRef="U007">4</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20190930"
      decimals="INF"
      id="Fact_8144a98eb4174391a5f3065f3f804da4"
      unitRef="U007">2</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_47bb69b206dc4e2ebd8789c0e31c814a">&lt;span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"&gt;The following is a summary of our investments (in thousands):&lt;/span&gt;
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zb56166283a7847d5befc091adecaa6a1" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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; font-weight: bold;"&gt;September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;752,495&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,484&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;753,831&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176,589&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176,865&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331,371&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;264&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331,618&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,986&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,963&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,297,389&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,073&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,299,225&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;539,820&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,108&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,767&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;106,536&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;101&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;106,500&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#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: 18pt; 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;34,692&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;(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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,654&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,283&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,302&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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;690,331&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,234&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(342&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', 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;693,223&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,987,720&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,307&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(579&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,992,448&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,988,932&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;5,307&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,993,054&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zf8befa7024ac4c7aaab0e6b0e3be21d5" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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; font-weight: bold;"&gt;December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Cost &lt;/span&gt;(1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;956,879&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,858&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;955,034&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;168,839&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(104&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;168,738&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;244,640&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(77&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;244,578&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63,572&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(323&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63,249&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,433,930&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,362&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,431,599&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;299,018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;194&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,286&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;297,926&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;107,789&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;194&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(109&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;107,874&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,576&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,980&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;(287&lt;/div&gt;&lt;/td&gt;
    &lt;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;16,693&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;439,387&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;388&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,706&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438,069&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,873,317&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,068&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,869,668&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current 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;1,212&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,874,529&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;556&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,068&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,871,017&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze2689b040009421da56fad38f1ad9a5f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our available-for-sale securities are held at amortized cost.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4c2e520a6c644d0f8f16eee8ae381f87" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z94b340357ef0469db6ab0f6c9e7f6ab9" style="font-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;We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_5bd44b202ba0488e976f0c108e51d72a"
      unitRef="U002">752495000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_17a030f590644d8f919cc3773c831571"
      unitRef="U002">1484000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_12cd7dcada8d4d749dcdb38763dcfc9d"
      unitRef="U002">148000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_cd161d6d584f420ea5c9ba9bc949efac"
      unitRef="U002">753831000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_eab544f46afa456189480b40679240a9"
      unitRef="U002">176589000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_17d9194567ba4b81925f2f92660cef1f"
      unitRef="U002">321000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_100c8ffc20284501a343132ae0ed8437"
      unitRef="U002">45000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_98c570c1585942bea5d1f0188f766317"
      unitRef="U002">176865000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_1f3e39cc38284f8aad73189eea7bbf14"
      unitRef="U002">331371000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_55dede5be12f465e91cb1036a8898b74"
      unitRef="U002">264000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_c9141f4d41694e8689367b43adc2e88c"
      unitRef="U002">17000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_d3a9b4856c74472f9ddbaffca452fcbc"
      unitRef="U002">331618000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_9f527800450b4ccfad702bd8b0ced078"
      unitRef="U002">33986000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_8b5ee7831a314b079d162b364f8e4186"
      unitRef="U002">4000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_4c6fcccfdd674057a042456beb6f3b4d"
      unitRef="U002">27000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_a799e2ee1db54e1394e1dd3f2b81d089"
      unitRef="U002">33963000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_9015169599984f5a9691efcc7214ed32"
      unitRef="U002">2948000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_f8d38bdedc944fc0b4eb5d019b737d68"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_b8ed51c2f99b4ac79d540094c9b6e9b1"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_011150cb25224f2cb838d6f4cfff763a"
      unitRef="U002">2948000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_9801fd693cf84c299d17cb204de46d5f"
      unitRef="U002">1297389000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_34f6c8bc39f14366836a79be09b712d4"
      unitRef="U002">2073000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_066fd70a5e7f4cf9afd3f01bfd157e98"
      unitRef="U002">237000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_121922e704004fc1bdeee945857a1e7a"
      unitRef="U002">1299225000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_78a409a549ef459db614b179f7ae1230"
      unitRef="U002">539820000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_fabc4941e21c404ebacd6fdd93f57eee"
      unitRef="U002">3108000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_65ec80b321254172b0facb9181d06ab3"
      unitRef="U002">161000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_1d9754280ce9468db41a9c1e5804f2eb"
      unitRef="U002">542767000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ea15651e08bd4b8b990074a9aa80683d"
      unitRef="U002">106536000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_8cc45dce333042f88f9270fcb2c87584"
      unitRef="U002">101000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_22da9338810541e081cb24fd8d1addd4"
      unitRef="U002">137000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_bf708a036d044664bf01de902fd726fb"
      unitRef="U002">106500000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_bed56c4d2fcd4a74a0a1ccb2d57c9639"
      unitRef="U002">34692000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_ab2034269cfb4a7c85423cd3fab55733"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_bfeeeeed126d480cb63fc576abeed8ef"
      unitRef="U002">38000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_9c5f4db9e8c94424a80d08bf4752ae35"
      unitRef="U002">34654000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_a40f4d8491b24020962dbd41df0b3f94"
      unitRef="U002">9283000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_e8c2bf9cfc364442a2ce959566f9039c"
      unitRef="U002">25000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_291761b8778841229cce19ecec0f26b3"
      unitRef="U002">6000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_6d8b2363ee3e48939c0b94531ab5f6fb"
      unitRef="U002">9302000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_138aaf4a47a148d091cceb4ced2e1cfc"
      unitRef="U002">690331000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_7ca671875f59463da04bcd431895b579"
      unitRef="U002">3234000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_a3e30c4027b34e7188416b4d33de1f4d"
      unitRef="U002">342000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_43d557630d984789a8b9913da42427b3"
      unitRef="U002">693223000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_80f9e07c881d4103821ad1c51c0e34b7"
      unitRef="U002">1987720000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_58fe11e40d404aa1bab2f9bfb3e4d0cd"
      unitRef="U002">5307000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_155bd2a74c99447da52604b6e0c458ef"
      unitRef="U002">579000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20190930_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_1701ea613a34400c8d6e2580b27dc25d"
      unitRef="U002">1992448000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20190930"
      decimals="-3"
      id="Fact_1f42a3296a8a46159ca5daccd95f28b8"
      unitRef="U002">1212000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_bf6daa922cab48a5a56d8a8813257503"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_ca3f0a0ae7664efd944e9c8d18081b2f"
      unitRef="U002">606000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20190930"
      decimals="-3"
      id="Fact_d39acd6dd3b74a26881b8fe7d99c92de"
      unitRef="U002">606000</us-gaap:EquitySecuritiesFvNi>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost
      contextRef="c20190930"
      decimals="-3"
      id="Fact_7dd9273ab6134971a061f83f1f11e5f6"
      unitRef="U002">1988932000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain
      contextRef="c20190930"
      decimals="-3"
      id="Fact_f83b46d066b74393b302c03f0bf7f101"
      unitRef="U002">5307000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss
      contextRef="c20190930"
      decimals="-3"
      id="Fact_1127e05a95f04c3da8e856ad5d562421"
      unitRef="U002">1185000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi
      contextRef="c20190930"
      decimals="-3"
      id="Fact_f922c5a697914128981c946e313052fd"
      unitRef="U002">1993054000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_b181ed8da53647f8a6b292342a235f93"
      unitRef="U002">956879000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_bbd0aadb835946f18c00643e19a95d1b"
      unitRef="U002">13000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ef0125a302774eefaaa95d7cf7c879a0"
      unitRef="U002">1858000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_dbcc039edc834ac2bf7c0c255acc4867"
      unitRef="U002">955034000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_0187b54b654f4e109666c7737fc2551d"
      unitRef="U002">168839000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ab76344cef7f4d43993f5ff521643328"
      unitRef="U002">3000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_b4681433116b4d49be98ad2b8e89cc78"
      unitRef="U002">104000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_5e02db354e724de3836ccd8a4a92c759"
      unitRef="U002">168738000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_206242051e2c4d94b28d4e87712895a7"
      unitRef="U002">244640000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_6f0457f7164444eb8b1dc2704dc0f245"
      unitRef="U002">15000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_62d4d48225f74aaaad2a2ad0173aa452"
      unitRef="U002">77000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_71837a554d3c4531a97fafd18eaeac73"
      unitRef="U002">244578000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_1c044e91f5e742a3961b4f59ca6ef285"
      unitRef="U002">63572000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_7d3ea0c7354749eb97f7cc78122944ce"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_2fce21e0f698443099b81320b4220f73"
      unitRef="U002">323000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_c82b6d5a51574d56b98ea374c25e11c7"
      unitRef="U002">63249000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_15869a0e101243b38f48dfa9071509af"
      unitRef="U002">1433930000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_1a8eeeab3e9a48fc9b4e3403cac348d9"
      unitRef="U002">31000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_b203115e4d3d4e72b3822ecede585a5c"
      unitRef="U002">2362000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_d0ad541f93a44b54b3991471f048623d"
      unitRef="U002">1431599000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_f4ce593384ef4b7d83aad4901d4548b6"
      unitRef="U002">299018000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_a92b2d44b0c84e809a410e22bf4ced30"
      unitRef="U002">194000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_bf25c4a7182242d79e1b85dc2bf4e3a8"
      unitRef="U002">1286000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_7252bb5228e6422ea11010b94d8da62c"
      unitRef="U002">297926000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_9339c651e1c64d02a58d7ef8f3a401fa"
      unitRef="U002">107789000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_9617460cdd5b45769ba45c19086e38d7"
      unitRef="U002">194000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_4f98c3bc34da499abc8824624efb172c"
      unitRef="U002">109000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_22bb9a4b97cf4246b6dc9bd0962a5b27"
      unitRef="U002">107874000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_f4c2236cedf849b8971016981b4f39e6"
      unitRef="U002">15600000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_d0ce355fb70e47d5923fc09d2c261c75"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_c490dce6cb514f82bda4675e80f535b2"
      unitRef="U002">24000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_086c2ee40cf648798b812f56d1a08d40"
      unitRef="U002">15576000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_248f6769580b4861a0b529d0816594e0"
      unitRef="U002">16980000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_39e13e8a0ade405ea0ac29e4ae20285f"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_3c8a38bab38d41a4ae260eea177fe99e"
      unitRef="U002">287000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_ef07e7ef74ef4549a8bfa4cccef332d1"
      unitRef="U002">16693000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_2536445b56a5427d99424937cbc97ea6"
      unitRef="U002">439387000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_1eaf51b48a72465da90436695575076e"
      unitRef="U002">388000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_9735663a68094d99915263b97c19d53d"
      unitRef="U002">1706000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_2de2853621774dc4bfc77ca8feee79e3"
      unitRef="U002">438069000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_cb912863d431429d957f3c945ccb7b83"
      unitRef="U002">1873317000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_3e47e75bd6a34ec49729b7f1a089b5d8"
      unitRef="U002">419000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_7ad5d8e4832145f791a6f372b747c076"
      unitRef="U002">4068000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20181231_InvestmentTypeAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_fd5b6194ec48441eaeccfa14072ca7af"
      unitRef="U002">1869668000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20181231"
      decimals="-3"
      id="Fact_8433f3b9512246ac8207c5a05c776b60"
      unitRef="U002">1212000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20180101to20181231"
      decimals="-3"
      id="Fact_ff3617eb3aa949b3bb85ba97180ca782"
      unitRef="U002">137000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20180101to20181231"
      decimals="-3"
      id="Fact_c4705c14fdeb4bee9bbd4b73b126cd7a"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20181231"
      decimals="-3"
      id="Fact_43027ad4163e4bf48b6d2e208cc4225b"
      unitRef="U002">1349000</us-gaap:EquitySecuritiesFvNi>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost
      contextRef="c20181231"
      decimals="-3"
      id="Fact_db6494e7c50d4590bf5ea77988e0bd56"
      unitRef="U002">1874529000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain
      contextRef="c20181231"
      decimals="-3"
      id="Fact_da3c037eece345dbb273716db26a5d65"
      unitRef="U002">556000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss
      contextRef="c20181231"
      decimals="-3"
      id="Fact_0046e705d988481bb8e3da035ffe5c60"
      unitRef="U002">4068000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi
      contextRef="c20181231"
      decimals="-3"
      id="Fact_a9c78208c74f4e24ae95c6752970f890"
      unitRef="U002">1871017000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi>
    <us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_0f4958e928884c1e9dea3a20663a4c54">
&lt;div style="display:none;"&gt;&lt;br/&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 we consider to be temporarily impaired at September 30, 2019. 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;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z78a191fc6a1c47b5bbf4c2cc8e099df3" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" 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;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;(In thousands)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;104&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;304,705&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(268&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,675&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(41&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;336,380&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(309&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF; 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%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;102,733&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(156&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,974&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(26&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;125,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,918&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(55&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,918&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(55&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF; 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,498&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,597&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,095&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(33&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;486,854&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(480&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,246&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(99&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;557,100&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(579&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock>
    <us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="0"
      id="Fact_51b806ebffcc49c38f9a73201a064390"
      unitRef="U010">104</us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_0bc2c883bb864c4089ece35a15919bc3"
      unitRef="U002">304705000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_83fd90d887664061be0bf9e1b69269ca"
      unitRef="U002">268000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_090ecc716c20432ba4efc5ca41020612"
      unitRef="U002">31675000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_0291f3ece3d144e99e18bb05d715d423"
      unitRef="U002">41000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_df78e61e593749bdabb662abf7265e25"
      unitRef="U002">336380000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_595a90051f0743fb8d4f51d27e54a83a"
      unitRef="U002">309000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="0"
      id="Fact_e08462cb68ac49b3b3c3359e5d770016"
      unitRef="U010">28</us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_cef3c9031cb54a4c9a576cfd6bb25f14"
      unitRef="U002">102733000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_c24473498a7b43398e845fd91e459c33"
      unitRef="U002">156000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_3ae3c388e9a24270a821209f160a096b"
      unitRef="U002">22974000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_8fe83f9b7aaf4ad6a7714928869b9022"
      unitRef="U002">26000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_4fa18bf2ef50415e95791a938f030095"
      unitRef="U002">125707000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_25d35726c1ac4e569f145f5fac73d67b"
      unitRef="U002">182000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="0"
      id="Fact_55d09cb2246149c9b30a133e2a92a05c"
      unitRef="U010">9</us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_06735049f9934ec68599825699814a3f"
      unitRef="U002">77918000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_4dc4d63e1a724eecb8a92758026dd667"
      unitRef="U002">55000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_366d3d1a14dc46af8ca33eee848e6ef9"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_f463e65cbe1946d3a63d082c9b137caf"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_f3ea8fadc6484ec591933cb40c3852ea"
      unitRef="U002">77918000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_30c82f5c0cc2433686b8fda2508a4229"
      unitRef="U002">55000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="0"
      id="Fact_373b2ec7bfcb4e44be7a438d30c91ea3"
      unitRef="U010">13</us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_e6f5865e27de4dbc86e5f379535eea9b"
      unitRef="U002">1498000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_d12d239121ea48fa95cdbee79c23f439"
      unitRef="U002">1000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_294211c497a44b74b91d1241bde18b03"
      unitRef="U002">15597000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_0288bef87a724fcaa157b07c499a7e33"
      unitRef="U002">32000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_c479a7699515486899d6561160d554b1"
      unitRef="U002">17095000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss
      contextRef="c20190930_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_d586a1ba946e4a7c9681158315aba90b"
      unitRef="U002">33000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1
      contextRef="c20190930"
      decimals="0"
      id="Fact_06f7abbf000f49eabde6e2071d5866cd"
      unitRef="U010">154</us-gaap:AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue
      contextRef="c20190930"
      decimals="-3"
      id="Fact_b2bbc700ee75493eb9cd50059005c4e4"
      unitRef="U002">486854000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20190930"
      decimals="-3"
      id="Fact_2b41934b661649a49df3fd610175613e"
      unitRef="U002">480000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue
      contextRef="c20190930"
      decimals="-3"
      id="Fact_73bb0ba4579d45e58b41562b4b52041a"
      unitRef="U002">70246000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionTwelveMonthsOrLongerFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20190930"
      decimals="-3"
      id="Fact_099dab2dd40b4d0fafc8c7b94d5e2019"
      unitRef="U002">99000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue
      contextRef="c20190930"
      decimals="-3"
      id="Fact_13d5b5d23b744127821937d7996a7021"
      unitRef="U002">557100000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionFairValue>
    <us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss
      contextRef="c20190930"
      decimals="-3"
      id="Fact_166f0b63c83849f2badec28280087aac"
      unitRef="U002">579000</us-gaap:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:FairValueDisclosuresTextBlock
      contextRef="c20190101to20190930"
      id="Text_e78cc309d33646e099bb096d906cddfa">
&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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We 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 the majority 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following tables present the major security types we held at &lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that we regularly measure and carry at fair value. At &lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;our ProQR investment was &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions that extend to the fourth quarter of 2019; as a result, we&lt;/span&gt; included a lack of marketability discount in valuing this investment, which is a Level 3 input.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; The amount we owned in ProQR did not change from &lt;/span&gt;December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The tables below segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="ze035bc9b78a548a8a5fdecd96869b42a" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;202,904&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;202,904&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,296,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,296,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;283,365&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;283,365&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366,272&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366,272&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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 (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;43,265&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;43,265&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&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;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div&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%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (5)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: 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: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,195,958&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;569,176&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,626,176&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z210039b332e745bb8548fc2512c58d45" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;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, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;146,281&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;146,281&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (6)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,252,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,252,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;276,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#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;276,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;260,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;260,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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 (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;79,942&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;79,942&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&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;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (5)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,017,298&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;406,435&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,609,514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt; 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbee9abbccdd54e73807b84f4e3b2b782" style="font-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.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z438bdc6881aa4cb99b165b8919727dda" style="font-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;$16.6 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4a15bc1d737a430282eea21dc5b0bfb3" style="font-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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3864b9dae47f4db89495ac682873943c" style="font-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;$3.0 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb45245eabfe741ed8a9fa3ca3dc821f5" style="font-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;Included in other current assets.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd2f62bfc179a4c6ea80ab9be8baa40fe" style="font-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;$50.2 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28e1624d992e41cbb67711b300f91fbe" style="font-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;$14.2 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div 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 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 1 percent notes had a fair value of $783.7 million at September 30, 2019. 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="c20190101to20190930"
      id="Text_d5bf395e71d644c394d9e335eb3fe054">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following tables present the major security types we held at &lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that we regularly measure and carry at fair value. At &lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;our ProQR investment was &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;subject to trading restrictions that extend to the fourth quarter of 2019; as a result, we&lt;/span&gt; included a lack of marketability discount in valuing this investment, which is a Level 3 input.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; The amount we owned in ProQR did not change from &lt;/span&gt;December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The tables below segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="ze035bc9b78a548a8a5fdecd96869b42a" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;At&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;202,904&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;202,904&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,296,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,296,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;283,365&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;283,365&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366,272&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366,272&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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 (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;43,265&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;43,265&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&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;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div&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%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,948&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (5)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: 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: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,195,958&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;569,176&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,626,176&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;606&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z210039b332e745bb8548fc2512c58d45" style="font-family: 'Times 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;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;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, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;146,281&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;146,281&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (6)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,252,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,252,960&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;276,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#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;276,612&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#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%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;260,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;260,154&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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 (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;79,942&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;79,942&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&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;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (5)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,017,298&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;406,435&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,609,514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,349&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt; 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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbee9abbccdd54e73807b84f4e3b2b782" style="font-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.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z438bdc6881aa4cb99b165b8919727dda" style="font-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;$16.6 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4a15bc1d737a430282eea21dc5b0bfb3" style="font-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 style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3864b9dae47f4db89495ac682873943c" style="font-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;$3.0 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb45245eabfe741ed8a9fa3ca3dc821f5" style="font-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;Included in other current assets.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd2f62bfc179a4c6ea80ab9be8baa40fe" style="font-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;$50.2 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28e1624d992e41cbb67711b300f91fbe" style="font-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;$14.2 million was included in cash and cash equivalents, with the difference included in short-term investments.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_3e8681d673cb4651bd1fa1b44eaab381"
      unitRef="U002">202904000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_e5fd125d4ce14e01ba945d09c22ca8f1"
      unitRef="U002">202904000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_2ae7973768e94bfc95e7ace04ee2ee57"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_f06c4a25a92d4d4c8de1315bf85fd8ba"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_26191d5384f64272905581a8fe8b850e"
      unitRef="U002">1296598000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_a95f5ccf79e94eacb1104c5c32c16f2c"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_005ea5438f1a425e8a7d2f6ca3f789f8"
      unitRef="U002">1296598000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_971bf29f6c974f35892eafb721742e6e"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_31607d0464414d63a9d40c3bda86cebd"
      unitRef="U002">283365000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_e26d4a39eb374d97a569b01baf57ac91"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_66ce550478994d1888c51ee65d3e1f4b"
      unitRef="U002">283365000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_b25daef28f5b47418fe2948e4af478a7"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_7e9a01d143344a90abd0d3c282087ea8"
      unitRef="U002">366272000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_74bd8f38d6cb4e46a4682239ac10752a"
      unitRef="U002">366272000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_0a74a6aa5ded432f9a25a4dd4c8ff5f1"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_2c1c07732dce41c1a5692ffaf6f7eb8c"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_719745a58a2745968c9eec989ba98101"
      unitRef="U002">43265000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_7d0b724cbe6b447fbe815dfa3325c1bf"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_a74935eb997046d5b5e3885e886e4c50"
      unitRef="U002">43265000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_7c85b2b200b64b4192a661395ad16c98"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_d28150ca7b45448fa25fbb6cd2de43d0"
      unitRef="U002">2948000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_5a61795ec459452ead9ddd38ac0001dc"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_1a9f64e6bb854352a0cc51103b746ffb"
      unitRef="U002">2948000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_88b4fe6d399242d7afa665095fb970ae"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_df377b1e9061452b8f3d582001e6a515"
      unitRef="U002">606000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_bf12a1b598f8409895330f9066de1b32"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_ad99c2d1e5a94c5ba9d5a036cc502ad7"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_27206d10cda844678b9284a21f0089ac"
      unitRef="U002">606000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20190930_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_a331dc8e64f14efa9335022e05100a1b"
      unitRef="U002">2195958000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_e1395942b9544480802a3d41ed25d304"
      unitRef="U002">569176000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_51287e35ae9647498fd94416292e645c"
      unitRef="U002">1626176000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20190930_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_6c77bc755d97480da91f20c3c22c51d6"
      unitRef="U002">606000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_57ccf9920b8146f388ce592d258d1e8f"
      unitRef="U002">146281000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_fea6987da44d4b7b9ae95d3cbe838bac"
      unitRef="U002">146281000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_84311542bec446b5ae4092e88c1dc39c"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_d3a3f525a776438d93d0f6cd6072a582"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_d2cf55f51c9147beb6d1c06acf8ed2dc"
      unitRef="U002">1252960000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_4119dc6c174e4de8b86dd778da98348e"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_7d8b8702ebaa49688da5775fe3f37558"
      unitRef="U002">1252960000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ed3e7cbd1aa24ea4950df980878d1f0b"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_303ee7acffb64b30b37958792583e02d"
      unitRef="U002">276612000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ada275bc1e4f439cb01075d0aa3db7b1"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_50adb0366138423898f832093af4dabf"
      unitRef="U002">276612000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_dd2e5cc835fe4294b9a304420fef7c35"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_6e8ff7ac339a47ee87988299df92fe42"
      unitRef="U002">260154000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_dc688c57298544adbac4c5b3cfbccac1"
      unitRef="U002">260154000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_78b4ceecb8ed42df949cfc7aeb36254e"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_e760b857f262426eb869bf7c46221388"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_cf2cd8ea24c34a298b35a62e5c63fe49"
      unitRef="U002">79942000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_cef740673b7c4b34ad1d1090f381a7ee"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_dd870cb48a2c41e1a286050af4d48831"
      unitRef="U002">79942000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_708e4a66c0db45a1856993da22f84254"
      unitRef="U002">0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_48764182e11a4bb5958ad2aaafc3c0c6"
      unitRef="U002">1349000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_188a62f9e68047bcb08308421c122a02"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_fc0cb8b8e77f46a3a979063a7dfedc7b"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_dbab2b6be37643578962200ba9475ea0"
      unitRef="U002">1349000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20181231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_ef2b12ca5e5b4853a44a965cf2a0461c"
      unitRef="U002">2017298000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_b34b60c6b5eb4dfdbfd60019ed7589b9"
      unitRef="U002">406435000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_f797a4c0b00e4af6b8ed32a98a8235e3"
      unitRef="U002">1609514000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20181231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_d7e10e063db449559b0596c6cc218dbb"
      unitRef="U002">1349000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-5"
      id="Fact_08e330d1065a49519e95b71b1366c2a4"
      unitRef="U002">16600000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20190930_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-5"
      id="Fact_ee5972ccabd947f08e866af02ecd032a"
      unitRef="U002">3000000.0</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-5"
      id="Fact_37b19471b2774b12872f273581f1a2fc"
      unitRef="U002">50200000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:AvailableForSaleSecurities
      contextRef="c20181231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-5"
      id="Fact_555765ba22074b7c9579a23c07449fe0"
      unitRef="U002">14200000</us-gaap:AvailableForSaleSecurities>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_4535354b3f1643ae9324af29ecc7467d"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:NotesPayableFairValueDisclosure
      contextRef="c20190930_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member"
      decimals="-5"
      id="Fact_08dde5b870bf48ad8f56230371fe5c23"
      unitRef="U002">783700000</us-gaap:NotesPayableFairValueDisclosure>
    <us-gaap:LesseeOperatingLeasesTextBlock
      contextRef="c20190101to20190930"
      id="Text_d5c8c3f120884a79a71b128c745e4df5">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&#160; Operating Leases&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease with an initial term ending in June 2021 and an option to extend the lease for up to two&#160;five-year periods.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also lease additional office space and we sublease a portion of this space to Akcea. We lease this space under a non-cancelable operating lease with an initial term ending in June 2023 and an option to extend the lease for one&#160;five-year period. The sublease with Akcea is eliminated in our condensed consolidated financial statements.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;Akcea entered into an operating lease agreement for office space located in Boston, Massachusetts for its new corporate headquarters in the second quarter of 2018. The lease commencement date was in August 2018 and Akcea took occupancy in September 2018. Akcea is leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an additional five-year term. Under the lease agreement, Akcea received a three-month free rent period, which commenced on August 15, 2018, and a tenant improvement allowance up to $3.8 million. Akcea provided the lessor with a letter of credit to secure its obligations under the lease in the initial amount of $2.4 million, to be reduced to $1.8 million on the third anniversary of the rent commencement date and to $1.2 million on the fifth anniversary of the rent commencement date if Akcea meets certain conditions set forth in the lease at each such time.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include the extension options for these leases.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zf42106fcdfa447c3a605f18b4bb6c5cc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: center;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;At September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#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: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use operating lease assets (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average remaining lease term&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average discount rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z134ddf538270485d8e34269956271e23" style="font-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 deposits and other assets on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb6759401030e41a8ab46de882c820315" style="font-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;Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the nine months ended&#160;September 30, 2019, we paid $2.9 million of rent payments, which was included in operating activities in our condensed consolidated statement of cash flows.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of September 30, 2019, the payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zb029d562d7d14830957cb4fe63551490" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Remainder of 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;801&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Years ending December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,282&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,781&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,520&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,861&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total minimum lease payments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,264&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Imputed interest&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,533&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating lease liabilities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,731&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Rent expense was $0.8 million and $1.0 million for the three months ended September 30, 2019 and 2018, respectively. Rent expense was $2.7 million and $1.8 million for the nine months ended&#160;September 30, 2019 and 2018, respectively.&lt;/div&gt;
</us-gaap:LesseeOperatingLeasesTextBlock>
    <ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease
      contextRef="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember"
      decimals="INF"
      id="Fact_1329e55da4b24760858cff0f1661423a"
      unitRef="U011">2</ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeAndLaboratorySpaceAdjacentToManufacturingFacilityMember"
      id="Fact_d173eb748a4244ab9218fe6c1006c150">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease
      contextRef="c20190101to20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember"
      decimals="INF"
      id="Fact_e9ff44ffc86e4cc792faf91f29186330"
      unitRef="U011">1</ions:LesseeLeasingArrangementsOperatingLeasesNumberOfOptionsToExtendLease>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20190930_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceSubleasedToAkceaTherapeuticsIncMember"
      id="Fact_89235ac20a9447e28844342f084f8e0f">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      id="Fact_b4040ba6c3a5449ca0431c78dadcc6f7">P123M</us-gaap:LesseeOperatingLeaseTermOfContract>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      id="Fact_a62715aca02b493c9c7ae5090e0245e5">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeOperatingLeasePeriodOfFreeRent
      contextRef="c20190101to20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      id="Fact_cf16c83c2adb47f3bbf9d36201ccc3d1">P3M</ions:LesseeOperatingLeasePeriodOfFreeRent>
    <ions:LesseeOperatingLeaseAllowanceForTenantImprovements
      contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      decimals="-5"
      id="Fact_536a376ef364487fab6f3719c345245d"
      unitRef="U002">3800000</ions:LesseeOperatingLeaseAllowanceForTenantImprovements>
    <ions:LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation
      contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      decimals="-5"
      id="Fact_c72b744673274b47a98716e4aa4f4f08"
      unitRef="U002">2400000</ions:LesseeOperatingLeaseInitialLetterOfCreditToSecureLeaseObligation>
    <ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate
      contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      decimals="-5"
      id="Fact_0de0396ac4ed487d9be0855964bf2ad1"
      unitRef="U002">1800000</ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnThirdAnniversaryOfRentCommencementDate>
    <ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate
      contextRef="c20190930_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_PropertyPlantAndEquipmentByTypeAxis_OfficeSpaceForCorporateHeadquartersMember"
      decimals="-5"
      id="Fact_353e61b09a0c4f77b8aaa58598b878ac"
      unitRef="U002">1200000</ions:LesseeOperatingLeaseLetterOfCreditToSecureLeaseObligationOnFifthAnniversaryOfRentCommencementDate>
    <ions:LesseeOperatingLeaseInformationTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_ec59cccffe8f4df08b9f20cfc91b55a6">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;

&lt;div 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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zf42106fcdfa447c3a605f18b4bb6c5cc" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: center;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;At September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#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: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use operating lease assets (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average remaining lease term&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average discount rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z134ddf538270485d8e34269956271e23" style="font-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 deposits and other assets on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"&gt;&lt;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb6759401030e41a8ab46de882c820315" style="font-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;Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</ions:LesseeOperatingLeaseInformationTableTextBlock>
    <us-gaap:OperatingLeaseRightOfUseAsset
      contextRef="c20190930"
      decimals="-5"
      id="Fact_3068d59045b74301b2c28fc3dfb6b8be"
      unitRef="U002">13000000.0</us-gaap:OperatingLeaseRightOfUseAsset>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20190930"
      decimals="-5"
      id="Fact_fbe5ecbb80b44b659c35900b4d87399c"
      unitRef="U002">17700000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1
      contextRef="c20190930"
      id="Fact_979be86519a0452db35a7400c2b1c9a0">P8Y3M18D</us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1>
    <us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent
      contextRef="c20190930"
      decimals="3"
      id="Fact_877f6ec0003e46b59290f627dcea6e25"
      unitRef="U003">0.075</us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent>
    <us-gaap:OperatingLeaseLiabilityCurrent
      contextRef="c20190930"
      decimals="-5"
      id="Fact_04c209b55cd343c495d9204a38815493"
      unitRef="U002">2100000</us-gaap:OperatingLeaseLiabilityCurrent>
    <us-gaap:OperatingLeasePayments
      contextRef="c20190101to20190930"
      decimals="-5"
      id="Fact_a2930947c0364634811e32f2e71b5292"
      unitRef="U002">2900000</us-gaap:OperatingLeasePayments>
    <us-gaap:ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock
      contextRef="c20190101to20190930"
      id="Text_755569525bde4238abc938fe9a8e90e4">
&lt;div style="display:none;"&gt;&lt;br/&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 September 30, 2019, the payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zb029d562d7d14830957cb4fe63551490" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Remainder of 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;801&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Years ending December 31,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,282&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,781&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,520&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,861&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total minimum lease payments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,264&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Imputed interest&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,533&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating lease liabilities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,731&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfFutureMinimumLeasePaymentsForCapitalLeasesTableTextBlock>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths
      contextRef="c20190930"
      decimals="-3"
      id="Fact_b172fcbc56fa449ca8d311d79522445f"
      unitRef="U002">801000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo
      contextRef="c20190930"
      decimals="-3"
      id="Fact_f4a841c5f2a14915b26977cb0a43cc9b"
      unitRef="U002">3282000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree
      contextRef="c20190930"
      decimals="-3"
      id="Fact_cff84cd8c71846e3b68b3b54a1d69862"
      unitRef="U002">3019000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour
      contextRef="c20190930"
      decimals="-3"
      id="Fact_af6fa6ab476b4157b441eb23c40c8d5c"
      unitRef="U002">2781000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive
      contextRef="c20190930"
      decimals="-3"
      id="Fact_40ac9e32ac7a4df78893b4b4cc07a061"
      unitRef="U002">2520000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive
      contextRef="c20190930"
      decimals="-3"
      id="Fact_95cde5b159734e08a7287dd63168ae8a"
      unitRef="U002">11861000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20190930"
      decimals="-3"
      id="Fact_6ecec3f1c18d49d6a5973d40b99d7e6e"
      unitRef="U002">24264000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount
      contextRef="c20190930"
      decimals="-3"
      id="Fact_76416dec037740b29c18f75520e91e34"
      unitRef="U002">6533000</us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20190930"
      decimals="-3"
      id="Fact_8ca379c9d8b245ba84f4ee7d1b392918"
      unitRef="U002">17731000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20190701to20190930"
      decimals="-5"
      id="Fact_a6f852dadc68455e9cc7cb478d765cce"
      unitRef="U002">800000</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20180701to20180930"
      decimals="-5"
      id="Fact_462f8023ee66421ba3d584c023ecf0c0"
      unitRef="U002">1000000.0</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20190101to20190930"
      decimals="-5"
      id="Fact_47f9cb5356444e72803cedfffb66b467"
      unitRef="U002">2700000</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20180101to20180930"
      decimals="-5"
      id="Fact_48776725679644ff8dd1226f92cf1642"
      unitRef="U002">1800000</us-gaap:OperatingLeaseExpense>
    <us-gaap:IncomeTaxDisclosureTextBlock
      contextRef="c20190101to20190930"
      id="Text_8233d9a1816040bf91b26046eab26a3f">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -45pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6.&#160; Income Taxes&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 24.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded an income tax benefit of $14.9 million and an income tax expense of $9.2 million for the three and nine months ended&#160;September 30, 2019, compared to income tax expense of $0.5 million and $0.8 million for the same periods in 2018, respectively. The tax benefit recorded for the three months ended September 30, 2019 varies from what we would have recorded using the U.S. federal statutory rate primarily due to a state tax benefit resulting from our combined state tax filings with Akcea, estimated R&amp;amp;D and orphan drug credits, excess tax benefits related to share-based compensation and a benefit related to a change in the estimated tax value of Akcea shares we received in 2018. The increase in our income tax expense for the nine months ended&#160;September 30, 2019, compared to the same period in 2018, was primarily due to our expectation that we will generate U.S. federal and state taxable income in 2019. We expect to utilize our deferred tax assets to partially offset our U.S. federal taxable income.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20190701to20190930"
      decimals="-5"
      id="Fact_8c6a908e6b65434bbf024e17428ebae8"
      unitRef="U002">-14900000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20190101to20190930"
      decimals="-5"
      id="Fact_fd1879cce1214f218a3342996ae53ea4"
      unitRef="U002">9200000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20180701to20180930"
      decimals="-5"
      id="Fact_3f21749a48134a59948ddf0a532aac46"
      unitRef="U002">500000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20180101to20180930"
      decimals="-5"
      id="Fact_e60a44889ada460787b6908260e5125e"
      unitRef="U002">800000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:CollaborativeArrangementDisclosureTextBlock
      contextRef="c20190101to20190930"
      id="Text_efed6362b719454ea6ffcb75e7594dba">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7.&#160; Collaborative Arrangements and Licensing Agreements&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Below, we have included our collaborations with substantive changes during the first nine months of 2019 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2018.&lt;/span&gt;&lt;/div&gt;

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

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

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

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

&lt;div style="display:none;"&gt;&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;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. In&lt;/span&gt; December 2017, we entered into a collaboration with Biogen to identify &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense medicines for the treatment of SMA&lt;/span&gt;. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We and Biogen are currently developing &lt;/span&gt;eight&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; medicines under collaborations, including medicines to treat people with ALS, Alzheimer&#x2019;s disease&lt;/span&gt;&lt;sub&gt;&#160;&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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 September 2019, we have received $&lt;/span&gt;2.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion from our Biogen collaborations, including $&lt;/span&gt;1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion we received from Biogen in the second quarter of 2018 for our 2018 strategic neurology collaboration.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z20353bec45cf4f6e84901f27ae49c055" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;107.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;104.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;234.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27.1pt; 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%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;58&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/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; font-weight: bold;"&gt;Neurology Collaborations&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2018 Strategic Neurology&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the second quarter of 2019, we achieved two $7.5 million milestone payments from Biogen when we advanced two new targets for unidentified neurological diseases&lt;sub&gt;&#160;&lt;/sub&gt;under this collaboration. These milestone payments did not create new performance obligations because they are part of our original R&amp;amp;D services performance obligation. Therefore, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation based on the percentage of completion. From inception through September 2019, we have included $582 million in payments in the transaction price for our R&amp;amp;D services performance obligation under this collaboration. We currently estimate we will satisfy our performance obligation in June 2028.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We will achieve the next payment of $7.5 million if Biogen designates another target under this collaboration.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2013 Strategic Neurology&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the third quarter of 2019, we achieved an $8 million milestone payment when Biogen initiated a Phase 1/2 study of ION859 (IONIS-LRRK2&lt;sub&gt;Rx&lt;/sub&gt;) &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for the treatment of people with Parkinson&#x2019;s disease &lt;/span&gt;under this collaboration. We concluded that this milestone payment was not related to our R&amp;amp;D services performance obligation. Therefore, we recognized the $8 million milestone payment in full in the third quarter of 2019 because we do not have any performance obligations related to this payment.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;From inception through September 2019, we have included $145 million in total payments in the transaction price for our R&amp;amp;D services performance obligation under this collaboration that we are recognizing over our estimated period of performance. We are recognizing revenue as we perform services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. In the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation. As of September 30, 2019, we have completed a&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; significant portion of the research and development services. We expect to complete the remainder of our services in 2020. &lt;/span&gt;As a result, we recorded a cumulative catch up adjustment of $16.5 million to decrease revenue in the third quarter of 2019. We will recognize this amount over the estimated remaining period we will perform services.&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2012 Neurology&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced IONIS-MAPT&lt;sub&gt;Rx &lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for Alzheimer&#x2019;s disease&lt;/span&gt; under this collaboration. This milestone payment did not create a new performance obligation because it is part of our performance obligation to conduct development of IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;. Therefore, we included the $7.5 million milestone payment in our transaction price for our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation. We are recognizing revenue for our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation based on the percentage of completion. From inception through September 2019, we have included $25.5 million in the transaction price for our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation. We currently estimate we will satisfy our performance obligation in September 2020.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have a separate performance obligation to perform R&amp;amp;D services under this collaboration. We have allocated $40 million in total payments to the transaction price for our R&amp;amp;D services performance obligation. In the third quarter of 2019, we completed our R&amp;amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. Biogen&#x2019;s decision to accept the development candidate was not within our control. We were recognizing revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected to satisfy our performance obligation. Because Biogen accepted the development candidate, we recognized $6.3 million of accelerated revenue in the third quarter of 2019.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We will achieve the next payment of up to $10 million if we advance a program under this collaboration.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;During the nine months of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Biogen collaborations, except as noted above.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our condensed consolidated balance sheet at September 30, 2019 and December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred revenue of $532.4 million and $580.9 million, respectively, related to our relationship with Biogen.&lt;/div&gt;

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

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

&lt;div 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;Bayer&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize our programs targeting FXI for the treatment of clotting disorders. In October 2019, Bayer decided it would advance IONIS-FXI-L&lt;sub&gt;Rx&lt;/sub&gt; following positive clinical results and we earned a $10 million milestone payment. At September 30, 2019, we determined that it was not probable that we could earn this milestone payment. As such, we did not recognize any revenue associated with it during the third quarter of 2019. Bayer is now responsible for all global development, regulatory and commercialization activities and costs for the FXI program. From inception through September 2019, we have received over $175 million from our Bayer collaboration, not including the $10 million milestone payment we earned in the fourth quarter of 2019.&#160; We will achieve the next payment of $20 million when Bayer initiates a Phase 3 study under the FXI program.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK includes two drugs targeting hepatitis B virus, or HBV: IONIS-HBV&lt;sub&gt;Rx&lt;/sub&gt; and IONIS-HBV-L&lt;sub&gt;Rx&lt;/sub&gt;, which we designed to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program, for which we earned a $25 million license fee. From inception through September 2019, we have received more than $164 million in payments under our collaboration with GSK, not including the $25 million license fee, which we expect to receive in the fourth quarter of 2019. We will achieve the next payment of $15 million when GSK initiates a Phase 3 study for a drug under this program.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We identified a new performance obligation when we granted GSK the license of the HBV program and assignment of related intellectual property rights in the third quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $25 million license fee for the HBV program as revenue at that time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z2a013d4519bd47b387164e642d8d6b5c" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any deferred revenue from our relationship with GSK at September 30, 2019 or December 31, 2018.&lt;/div&gt;

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

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

&lt;div style="display:none;"&gt;&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;We have &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; collaborations with Roche, &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to develop treatments for Huntington's disease, or HD, and &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;develop IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases. In December 2017, upon completion of the Phase 1/2 study of IONIS-HTT&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Roche exercised its option to license IONIS-HTT&lt;/span&gt;&lt;sub&gt;Rx &lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;and is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. In October 2018, we entered into a collaboration agreement with Roche to&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for the treatment of complement-mediated diseases. The first indication we plan to pursue is the treatment of patients with geographic atrophy, or GA, the advanced stage of dry age-related macular degeneration, or AMD. We are responsible for conducting a Phase 2 study in patients with dry AMD. In addition, we plan to evaluate the medicine for a severe and rare renal indication. &lt;/span&gt;Roche&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; has the option to license IONIS-FB-L&lt;/span&gt;&lt;sub&gt;&lt;span style="background-color: #FBFBFB;"&gt;Rx&lt;/span&gt;&lt;/sub&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; at the completion of these studies. Upon licensing, &lt;/span&gt;Roche &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;will be responsible for all further global development, regulatory and commercialization activities and costs.&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through June 2019, we have received over $&lt;/span&gt;220&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million from our Roche collaborations, including $&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;milestone payments we earned in the first quarter of 2019 when Roche dosed the first patient in a Phase 3 study for IONIS-HTT&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We will achieve the next payment of $&lt;/span&gt;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if Roche advances IONIS-HTT&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z5a49728eb04942b281219a3239b033e8" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our revenue in the first nine months of 2019 included $35 million of milestone payments we earned when Roche dosed the first patient in the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt; in the first quarter of 2019. We recognized these milestone payments in full in the first quarter of 2019 because we do not have any performance obligations related to these milestone payments, as Roche is conducting the Phase 3 study of IONIS-HTT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;During the first nine months of 2019, we did not have any changes to our performance obligations or the timing in which we expect to recognize revenue under our Roche collaborations.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our condensed consolidated balance sheet at September 30, 2019 and December 31, 2018&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred revenue of $56.7 million and $72.6 million, respectively, related to our relationship with Roche.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under this collaboration agreement. We reflect the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock in a separate line on the statement of operations and a separate line within stockholders&#x2019; equity in our condensed consolidated balance sheet.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and AKCEA-APOCIII-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;sub&gt;&#160;&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and AKCEA-APOCIII-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the FDA and providing initial quantities of API for each medicine. If Novartis exercises an option for either of these medicines, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such medicine. &lt;/span&gt;In the first quarter of 2019, Novartis licensed AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;. Novartis is responsible for conducting and funding all future development, regulatory and commercialization activities for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt;, including a global pivotal cardiovascular outcomes study, for which planning and initiation activities are underway. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through September 2019, we have received over $&lt;/span&gt;343&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million from our Novartis collaboration, including $&lt;/span&gt;150&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we earned from Novartis in the first quarter of 2019 for the license of AKCEA-APO(a)-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;. Akcea paid us $75 million as a sublicense fee in 2.8 million shares of Akcea common stock.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We identified a new performance obligation when we granted Novartis the license of AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; in the first quarter of 2019 because the license is distinct from our other performance obligations. We recognized the $150 million license fee for AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; as revenue at that time because Novartis had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Novartis.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;Novartis has the option to purchase additional API of AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; in the future at agreed upon terms and conditions under our collaboration agreement. We identified a new performance obligation when we delivered additional AKCEA-APO(a)-L&lt;sub&gt;Rx&lt;/sub&gt; API to Novartis in the third quarter of 2019 because the delivery of the API is distinct from our other performance obligations. We recognized $5.5&#160; million in revenue for the API we sold to Novartis in the third quarter of 2019.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea is responsible for the development activities under this collaboration. As such, Akcea is recognizing the associated revenue in its statement of operations, and we reflect all of Akcea&#x2019;s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core operating segment results and Akcea recognizes the fees as R&amp;amp;D expense. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our condensed consolidated balance sheet.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zd0e86e09a7c74df9a1e6577ab1ae4307" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the first nine months of 2019, we did not have any changes to our performance obligations, except as noted above, or the timing in which we expect to recognize revenue under our Novartis collaboration.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;Our condensed consolidated balance sheet at September 30, 2019 and December 31, 2018 included deferred revenue of $10.8 million and $28.8 million, respectively, related to our relationship with Novartis.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2019, Akcea initiated a collaboration with Pfizer for the license of AKCEA&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;-ANGPTL3-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt; to treat people with cardiovascular and metabolic diseases. Akcea is currently conducting a Phase 2 study of AKCEA&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;-ANGPTL3-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of non-alcoholic fatty liver disease, or NAFLD. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the ongoing Phase 2 study.&lt;/div&gt;

&lt;div style="display:none;"&gt;&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;Under the terms of the agreement, Akcea will receive a $&lt;/span&gt;250&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront license fee, upon closing the transaction, including receiving Hart-Scott Rodino clearance. Akcea is also eligible to receive development, regulatory and sales milestone payments of up to $&lt;/span&gt;1.3&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion and tiered royalties in the mid-teens to low-&lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; range on annual worldwide net sales. Akcea has retained the rights to co-commercialize AKCEA&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;-ANGPTL3-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in the U.S. and certain additional markets. The license fee, milestone payments and royalties will be split equally between us and Akcea. Upon receipt of the upfront payment from Pfizer&lt;/span&gt;, Akcea expects to pay us its $125 million sublicense fee in 6.9 million shares of Akcea common stock.&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In October 2019, Akcea initiated a collaboration with Pfizer for the license of AKCEA&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;-ANGPTL3-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to treat people with cardiovascular and metabolic diseases. &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under the terms of the agreement, Akcea will receive a $&lt;/span&gt;250&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront license fee, upon closing the transaction, including receiving Hart-Scott Rodino clearance. &lt;/span&gt;Akcea is also eligible to receive development, regulatory and sales milestone payments of up to $1.3 billion and tiered royalties&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in the mid-teens to low-20 percent range &lt;/span&gt;on annual worldwide net sales. Akcea will pay us 50 percent of the license fee, milestone payments and royalties. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with the ongoing Phase 2 study. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Upon receipt of the upfront payment from Pfizer&lt;/span&gt;, Akcea expects to pay us its $125 million sublicense fee in 6.9 million shares of Akcea common stock.&lt;/div&gt;
</us-gaap:CollaborativeArrangementDisclosureTextBlock>
    <ions:NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="INF"
      id="Fact_92d0ca6977364d5fb2c03318547a94af"
      unitRef="U012">8</ions:NumberOfMedicinesCurrentlyInDevelopmentUnderCollaborations>
    <ions:CumulativePaymentsReceived
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-8"
      id="Fact_944abe169d7a466fb4caf185b29d5162"
      unitRef="U002">2300000000</ions:CumulativePaymentsReceived>
    <ions:UpfrontPaymentReceivedIncludingPurchaseOfStock
      contextRef="c20180401to20180630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="-9"
      id="Fact_0d14be9af67b4d4a829caea6fe74e573"
      unitRef="U002">1000000000</ions:UpfrontPaymentReceivedIncludingPurchaseOfStock>
    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      id="Text_a4df729ae7b348b986a98b4bee6e087a">
&lt;div style="display:none;"&gt;&lt;br/&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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z20353bec45cf4f6e84901f27ae49c055" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;107.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;104.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;234.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27.1pt; 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%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;58&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_58894b647a204f3f9befa22c21936367"
      unitRef="U002">81700000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_8ef36b11d0eb42bbb715301764db5835"
      unitRef="U002">70000000.0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_ea81f77e846e484588deec9130e7b93b"
      unitRef="U002">211900000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_842a3d9227b24a00849b1d5adf642f22"
      unitRef="U002">167700000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_214320278a344f3c9dcdf624651e18a3"
      unitRef="U002">25500000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_7513f535453a470d9ce60f657eb441e0"
      unitRef="U002">34800000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_2136a17c75884df48c7a85b6e0e70556"
      unitRef="U002">81900000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_da2c5324aca542a6a505108419820b49"
      unitRef="U002">66900000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_13c9d5dadf7e4112ba3699c18a26e515"
      unitRef="U002">107200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_fca0b727314b4479925799d29f853712"
      unitRef="U002">104800000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_3e28ae0133c44ae2852d1a6de979167d"
      unitRef="U002">293800000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_fe69625b03684bf9aab284fbd671bee2"
      unitRef="U002">234600000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="2"
      id="Fact_46a53177bab6411dbfa4bacef3eacf19"
      unitRef="U003">0.64</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="2"
      id="Fact_3f7d76bc791847c7bd8e878596274ee8"
      unitRef="U003">0.72</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="2"
      id="Fact_0f0eb4fc60434512b4407e359598effe"
      unitRef="U003">0.47</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="2"
      id="Fact_c6510891f3034be2ab38f94f3553a832"
      unitRef="U003">0.58</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfMilestonePaymentsAchieved
      contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="INF"
      id="Fact_306c661c02c04f9ebb9f4e44c4a3ef08"
      unitRef="U013">2</ions:NumberOfMilestonePaymentsAchieved>
    <ions:MilestonePaymentsReceived
      contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="-5"
      id="Fact_83943752e48341b1a621f6a843f1b50b"
      unitRef="U002">7500000</ions:MilestonePaymentsReceived>
    <ions:NumberOfNewTargetsAdvanced
      contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="INF"
      id="Fact_6cc814e8a72149c396b34a68306be938"
      unitRef="U014">2</ions:NumberOfNewTargetsAdvanced>
    <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation
      contextRef="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="-6"
      id="Fact_c9ca4f94b0054470b5d3b3df32d7d8ea"
      unitRef="U002">582000000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
    <ions:NextPotentialMilestonePayment
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember"
      decimals="-5"
      id="Fact_67f7f7f5b5c846b3bd36d59706671233"
      unitRef="U002">7500000</ions:NextPotentialMilestonePayment>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"
      decimals="-6"
      id="Fact_278c916db294450ba8ed188743359ff4"
      unitRef="U002">8000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_IONISLRRK2Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"
      decimals="-6"
      id="Fact_3af7c5f8c38b42e0a18b8c97fb956a41"
      unitRef="U002">8000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"
      decimals="-6"
      id="Fact_3ee9be7ea55d48379bcd6f6e6e3eca37"
      unitRef="U002">145000000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember"
      decimals="-5"
      id="Fact_26614eaf255c46349ca103734b10813b"
      unitRef="U002">-16500000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:MilestonePaymentsReceived
      contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"
      decimals="-5"
      id="Fact_9d2d8a0a28aa4ef487bf47e6509d20c5"
      unitRef="U002">7500000</ions:MilestonePaymentsReceived>
    <ions:MilestonePaymentsReceived
      contextRef="c20190401to20190630_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"
      decimals="-5"
      id="Fact_e04de81796d34701ac54d0d5074cc31e"
      unitRef="U002">7500000</ions:MilestonePaymentsReceived>
    <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation
      contextRef="c20190930_ProductOrServiceAxis_IONISMAPTMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"
      decimals="-5"
      id="Fact_f0eadc680d4f468eb5d90137253d596f"
      unitRef="U002">25500000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
    <ions:PaymentsIncludedInTransactionPriceForPerformanceObligation
      contextRef="c20190930_ProductOrServiceAxis_ResearchAndDevelopmentServicesMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"
      decimals="-6"
      id="Fact_f00ee12baddd4b159c3c46bb74880769"
      unitRef="U002">40000000</ions:PaymentsIncludedInTransactionPriceForPerformanceObligation>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"
      decimals="-5"
      id="Fact_35c6d90d51304a699ec0b4ff52f71fcd"
      unitRef="U002">6300000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NextPotentialMilestonePayment
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInDecember2012WithBiogenMember"
      decimals="-6"
      id="Fact_43169d472f8f443abcf67b8f14b7d246"
      unitRef="U002">10000000</ions:NextPotentialMilestonePayment>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_54ef69d3adc940c88647a751ad2a37ea"
      unitRef="U002">532400000</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember"
      decimals="-5"
      id="Fact_3014f578216c4b458dd9badfa79faf90"
      unitRef="U002">580900000</us-gaap:ContractWithCustomerLiability>
    <ions:MilestonePaymentEarned
      contextRef="c20191001to20191031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"
      decimals="-6"
      id="Fact_dc8c3107d8ce4ebdac270c3f0ff2ebcd"
      unitRef="U002">10000000</ions:MilestonePaymentEarned>
    <ions:CumulativePaymentsReceived
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"
      decimals="-6"
      id="Fact_effec1c7861e4fcaaf3668d229b3a3a9"
      unitRef="U002">175000000</ions:CumulativePaymentsReceived>
    <ions:MilestonePaymentEarned
      contextRef="c20191001to20191031_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"
      decimals="-6"
      id="Fact_e49028a7e92b4b55b48f4a1666cdf1c3"
      unitRef="U002">10000000</ions:MilestonePaymentEarned>
    <ions:NextPotentialMilestonePayment
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember"
      decimals="-6"
      id="Fact_bc59ef56d057411cac4515747dfabcd7"
      unitRef="U002">20000000</ions:NextPotentialMilestonePayment>
    <ions:NumberOfDrugsCurrentlyBeingAdvanced
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="INF"
      id="Fact_e5fe0235f431492d97bebbcd2963aeae"
      unitRef="U015">2</ions:NumberOfDrugsCurrentlyBeingAdvanced>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_f390941f4a55430abca54016f555f3e3"
      unitRef="U002">25000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:CumulativePaymentsReceived
      contextRef="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_58c2a122def94572b3276f3836cd2035"
      unitRef="U002">164000000</ions:CumulativePaymentsReceived>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_b9708436d19a450abd82842dddcbdaa4"
      unitRef="U002">25000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NextPotentialMilestonePayment
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_ef95c04dc3a44340bf6d97d697affc47"
      unitRef="U002">15000000</ions:NextPotentialMilestonePayment>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_LicenseMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_161ceddd95c4478eacc930db8d53cd82"
      unitRef="U002">25000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      id="Text_ca41bb95cd8b4b73a468aa7441b6fcf1">
&lt;div style="display:none;"&gt;&lt;br/&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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z2a013d4519bd47b387164e642d8d6b5c" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-5"
      id="Fact_62118ab0fb5d41899bb44d2f396b1371"
      unitRef="U002">25100000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-5"
      id="Fact_c32a477653cb42b3811095ae7c0b7a98"
      unitRef="U002">100000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-5"
      id="Fact_2b0d64696c9d44c7b8cc9d051d50e372"
      unitRef="U002">25300000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-5"
      id="Fact_f9c94c8a3fa4457f848c945c207a2aa7"
      unitRef="U002">1500000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="2"
      id="Fact_86ab793c4c224a73978fdfde779f9da2"
      unitRef="U003">0.15</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="2"
      id="Fact_e499255f52504257b795c29f5829ad9b"
      unitRef="U003">0</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="2"
      id="Fact_d96294bd312f4da7823a8cf9ad798494"
      unitRef="U003">0.04</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="2"
      id="Fact_4d8e0ebf8aa94654a87ade66752b201a"
      unitRef="U003">0</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_376c42cf9e2f4f31b526f22998089e92"
      unitRef="U002">0</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMarch2010WithGSKMember"
      decimals="-6"
      id="Fact_01e151232773447992d835603dcc704f"
      unitRef="U002">0</us-gaap:ContractWithCustomerLiability>
    <ions:NumberOfCollaborationAgreements
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="INF"
      id="Fact_11cb1f3d6c7040af8c4d4c72dbbce13d"
      unitRef="U006">2</ions:NumberOfCollaborationAgreements>
    <ions:NumberOfCollaborationAgreements
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"
      decimals="INF"
      id="Fact_e8d6e2aa98a3466aac6e1aeaf1ccbc87"
      unitRef="U006">1</ions:NumberOfCollaborationAgreements>
    <ions:NumberOfCollaborationAgreements
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember"
      decimals="INF"
      id="Fact_ffdc56de69c144fc82abb9c50783b017"
      unitRef="U006">1</ions:NumberOfCollaborationAgreements>
    <ions:CumulativePaymentsReceived
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"
      decimals="-6"
      id="Fact_a75b275ae3ae4d478cf2ad99f17a9e99"
      unitRef="U002">220000000</ions:CumulativePaymentsReceived>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"
      decimals="-6"
      id="Fact_9a8c764ff07144f7add61d4cd70c3360"
      unitRef="U002">35000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NextPotentialMilestonePayment
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"
      decimals="-6"
      id="Fact_6ed199bf3e5f43e48862b62fa432c1b7"
      unitRef="U002">15000000</ions:NextPotentialMilestonePayment>
    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      id="Text_70f1cbc4bcf74b46a1a8e0b1b6ed1541">
&lt;div style="display:none;"&gt;&lt;br/&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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z5a49728eb04942b281219a3239b033e8" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="-5"
      id="Fact_0f6d4a3a012f4477984b11c4664e4b6c"
      unitRef="U002">4700000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="-5"
      id="Fact_b33165b5e9824fb5bba54918e9dbd6cb"
      unitRef="U002">1800000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="-5"
      id="Fact_40961bc844ef4352995937f4f432fdb8"
      unitRef="U002">52300000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="-5"
      id="Fact_3ef89c7313ad4f87aae1296cbcfa821c"
      unitRef="U002">5400000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="2"
      id="Fact_bdf875a68c1f4ffaa35dfa990f2a93f6"
      unitRef="U003">0.03</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="2"
      id="Fact_6691931c366f4281a20d83228c234ffd"
      unitRef="U003">0.01</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="2"
      id="Fact_f856f221a2b74ddf90b424d562484c0f"
      unitRef="U003">0.08</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="2"
      id="Fact_a5fbc85f1f0d43b38f7078592cf03649"
      unitRef="U003">0.01</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190331_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember"
      decimals="-6"
      id="Fact_773b279d63474cd5a044713ffc198719"
      unitRef="U002">35000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="-5"
      id="Fact_ae98e83e6d254226924f58b342e8f0e9"
      unitRef="U002">56700000</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsRocheMember"
      decimals="-5"
      id="Fact_3e86da011f2d4ec7bc14c905d451cb50"
      unitRef="U002">72600000</us-gaap:ContractWithCustomerLiability>
    <ions:CumulativePaymentsReceived
      contextRef="c20190930_RangeAxis_MinimumMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-6"
      id="Fact_3f1db703e5e04c3eba7f0303bd0307d8"
      unitRef="U002">343000000</ions:CumulativePaymentsReceived>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190331_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-6"
      id="Fact_8580e2d4500c4bcf9a63681481619efb"
      unitRef="U002">150000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:SublicenseFeePaidForLicenseOfDrug
      contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="-6"
      id="Fact_e1bd72cf7fb34dc588200203887e0e24"
      unitRef="U002">75000000</ions:SublicenseFeePaidForLicenseOfDrug>
    <ions:ReceiptOfSharesInSubsidiary
      contextRef="c20190101to20190331_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
      decimals="-5"
      id="Fact_feb287ac8b2c4388941e91c3a3a53636"
      unitRef="U001">2800000</ions:ReceiptOfSharesInSubsidiary>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190331_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-6"
      id="Fact_decb57be15eb48b3a29939a7a5584f39"
      unitRef="U002">150000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_AKCEAAPOALMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_a01e8b882d20413eae3ece2fe5028d14"
      unitRef="U002">5500000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20190101to20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      id="Text_2958b39c1bf14cc1be4632f290a898e3">
&lt;div style="display:none;"&gt;&lt;br/&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 and nine months ended September 30, 2019 and 2018, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zd0e86e09a7c74df9a1e6577ab1ae4307" style="font-family: 'Times 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;span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&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="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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Nine 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;September 30,&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-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;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176.3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_3e0980aa73dc4edeada62e83786fc5ae"
      unitRef="U002">8500000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_0fe401e466654d9cab7b60d1d2dc3b68"
      unitRef="U002">7200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_50de6a612bf04e37a6a54e6af77b30c3"
      unitRef="U002">176300000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_181b9eca967c4804bcde99ca0fe9283c"
      unitRef="U002">42700000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190701to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="2"
      id="Fact_45195fdcf03246e0b6e1bf53b6f66bf4"
      unitRef="U003">0.05</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180701to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="2"
      id="Fact_1c18cc9598c04ddb8417166c81b0ee40"
      unitRef="U003">0.05</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20190101to20190930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="2"
      id="Fact_52b3db77cbb04011bc85653e37a2c830"
      unitRef="U003">0.28</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20180101to20180930_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="2"
      id="Fact_61dbbb0a096542b984b1774803c875ef"
      unitRef="U003">0.10</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20190930_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_99ffee2d2b3a4cf2b2e69fbc5c919abd"
      unitRef="U002">10800000</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJanuary2017WithNovartisMember"
      decimals="-5"
      id="Fact_5d3b3d7795a9467497353204dc78ce44"
      unitRef="U002">28800000</us-gaap:ContractWithCustomerLiability>
    <ions:UpfrontLicenseFeeToBeReceived
      contextRef="c20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"
      decimals="-6"
      id="Fact_914e1de1479a4f0fa6a731f5fa0ae4c2"
      unitRef="U002">250000000</ions:UpfrontLicenseFeeToBeReceived>
    <ions:MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones
      contextRef="c20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"
      decimals="-8"
      id="Fact_50d6ac96e23442f48d9e722ee08e4747"
      unitRef="U002">1300000000</ions:MaximumAmountOfPaymentsReceivableForDevelopmentRegulatoryAndSalesMilestones>
    <ions:RoyaltyPercentageReceivedOnNetSalesOfDrug
      contextRef="c20191001to20191031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"
      decimals="2"
      id="Fact_03a58f57ace24d6da586c736b9b4ee05"
      unitRef="U003">0.20</ions:RoyaltyPercentageReceivedOnNetSalesOfDrug>
    <ions:SublicenseFeePaidForLicenseOfDrug
      contextRef="c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"
      decimals="-6"
      id="Fact_b96ff8c3b6274a80b59763786929eb14"
      unitRef="U002">125000000</ions:SublicenseFeePaidForLicenseOfDrug>
    <ions:ReceiptOfSharesInSubsidiary
      contextRef="c20191001to20191231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember_StatementScenarioAxis_ScenarioForecastMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2019WithPfizerMember"
      decimals="-5"
      id="Fact_5c440effcc5c4f1a9b78bc4e95d26a09"
      unitRef="U001">6900000</ions:ReceiptOfSharesInSubsidiary>
    <us-gaap:SegmentReportingDisclosureTextBlock
      contextRef="c20190101to20190930"
      id="Text_57f65420568e45369307ebb510015484">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;8.&#160; Segment Information&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We have &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; reportable segments, Ionis Core and Akcea Therapeutics. &lt;/span&gt;At September 30, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;we owned approximately 75 percent of Akcea.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Akcea is &lt;/span&gt;a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Akcea generates revenue from TEGSEDI and WAYLIVRA product sales and from its collaborations.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables show our segment revenue and income (loss) from operations for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands), respectively.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z0ad30f1f4f2a4ba8890de9668d5998f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81,672&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81,672&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,945&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,945&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;2,082&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83,618&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,081&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;95,699&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,165&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,543&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,515&lt;/div&gt;&lt;/td&gt;
    &lt;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;72,193&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,624&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,515&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167,892&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;119,147&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;53,215&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;165,369&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,636&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,591&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,478&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,523&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z1fe532a6dd9c40528713d7c7fce08810" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,010&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,010&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,746&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,956&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;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;82,756&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,105&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,241&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62,639&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,061&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;19,241&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(51,907&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;145,395&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;87,664&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84,249&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;163,967&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;90,397&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(65,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43,961&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(18,572&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc3a76d4662b34f2ea78dc5e6136dfb77" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,466&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;6,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,638&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;220,350&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,735&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;252,085&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;294,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176,328&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(94,007&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;376,833&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514,862&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,063&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(97,007&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;628,918&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;355,437&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;256,152&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,900&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;523,689&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;159,425&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(45,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,107&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,229&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zcf2b13dc1bb64910b74499773f3efba3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167,743&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167,743&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,432&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,232&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;177,175&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;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;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;181,975&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;232,850&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(49,936&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;225,584&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;410,025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(57,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;407,559&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;279,084&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;213,428&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12,796&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;479,716&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(158,758&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,340&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(72,157&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table shows our total assets by segment at September 30, 2019 and December 31, 2018 (in thousands), respectively.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z6c5c599a255e4059847439344a157872" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Assets&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;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;September 30, 2019&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,233,175&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;383,167&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(721,353&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2,894,989&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,975,491&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;365,261&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(672,968&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,667,784&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:SegmentReportingDisclosureTextBlock>
    <us-gaap:NumberOfReportableSegments
      contextRef="c20190101to20190930"
      decimals="INF"
      id="Fact_9dbbdc685892440db0d13157dc93e1ac"
      unitRef="U008">2</us-gaap:NumberOfReportableSegments>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20190930_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_8a08cad174d343278b9affb09890ce08"
      unitRef="U003">0.75</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock
      contextRef="c20190101to20190930"
      id="Text_c9763be15f2e4286b463292d699ff0e8">
&lt;div style="display:none;"&gt;&lt;br/&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 show our segment revenue and income (loss) from operations for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands), respectively.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z0ad30f1f4f2a4ba8890de9668d5998f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81,672&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;81,672&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,945&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,945&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;2,082&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83,618&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,081&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;95,699&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,165&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,543&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,515&lt;/div&gt;&lt;/td&gt;
    &lt;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;72,193&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,624&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,515&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167,892&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;119,147&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;53,215&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;165,369&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,636&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,591&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,478&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,523&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z1fe532a6dd9c40528713d7c7fce08810" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,010&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,010&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,746&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,956&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;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;82,756&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,105&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,241&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62,639&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,061&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;19,241&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(51,907&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;145,395&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;87,664&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84,249&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;163,967&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;90,397&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(65,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(43,961&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(18,572&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc3a76d4662b34f2ea78dc5e6136dfb77" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended September 30, 2019&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,884&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Product sales, net&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,466&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;6,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,638&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;220,350&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,735&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;252,085&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;294,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;176,328&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(94,007&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;376,833&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;514,862&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,063&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(97,007&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;628,918&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;355,437&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;256,152&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,900&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;523,689&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;159,425&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(45,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,107&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,229&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zcf2b13dc1bb64910b74499773f3efba3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Nine Months Ended September 30, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial revenue:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167,743&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;167,743&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,432&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,232&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;177,175&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;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,200&lt;/div&gt;&lt;/td&gt;
    &lt;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;181,975&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue under collaborative agreements&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;232,850&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(49,936&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;225,584&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total segment revenue&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;410,025&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,670&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(57,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;407,559&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total operating expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;279,084&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;213,428&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12,796&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;479,716&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130,941&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(158,758&lt;/div&gt;&lt;/td&gt;
    &lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,340&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(72,157&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table shows our total assets by segment at September 30, 2019 and December 31, 2018 (in thousands), respectively.&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: 12pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;br/&gt;&lt;/span&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z6c5c599a255e4059847439344a157872" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Assets&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;Ionis Core&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Akcea Therapeutics&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Elimination of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intercompany Activity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;September 30, 2019&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,233,175&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;383,167&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(721,353&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;2,894,989&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;December 31, 2018&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,975,491&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;365,261&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(672,968&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,667,784&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_53323a19912f41f5b876b834bbeff857"
      unitRef="U002">81672000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_5ca9c293944e4626b9c67249e8caf5c4"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_9e2db1c4f3e1470a93fb35f6c30b12df"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_b1ea86e8dcf041b1b04c06ed9580538e"
      unitRef="U002">81672000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_e86953f901094abb917df1ce9e7f1c5f"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_5361af2359594a0ca14fe4e63abb964c"
      unitRef="U002">11945000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_fe0d7a4ec93e45bda279181b743970cb"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_b5c41e8db8e7459e9599bf6248ece32f"
      unitRef="U002">11945000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_e78f66dbeecd4134b5696fb1e56fae5e"
      unitRef="U002">1946000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_cc8888b2e2ad4174a10dcde5ca08310e"
      unitRef="U002">136000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_0abeaa0269f44ffb8fdf5e7ebccfe360"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_e551e001dc374020a44354b8b11c0afd"
      unitRef="U002">2082000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_4d58f26f50fe4b34a3fd74381938cde6"
      unitRef="U002">83618000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_c67bc8aa4a8e44e8ad3eab68dc216d67"
      unitRef="U002">12081000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_1ea8d3e1655a40e4be55ea071097b4ff"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_ea8fba47d62f47e4905fab1189c26de9"
      unitRef="U002">95699000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_4c1402db490b4113af507188c310049a"
      unitRef="U002">69165000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_a6f7a37607aa4ca88f8ad9370426fb47"
      unitRef="U002">8543000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_c7248bf6d51a487191a956373a1d9bf0"
      unitRef="U002">-5515000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_fc5f98eb4c944d4293a1717df0086b82"
      unitRef="U002">72193000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_2623a77e02d44aea8daab02a515f0fd7"
      unitRef="U002">152783000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_b0bb8fdee4064bce8555c2ca8433b6be"
      unitRef="U002">20624000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_f117373797c94dee9191fa125aec4f1f"
      unitRef="U002">-5515000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_8e18850dea3e4a1da72f4ea97deea76e"
      unitRef="U002">167892000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:CostsAndExpenses
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_c3d5334cbb20457ba631760a2c28be98"
      unitRef="U002">119147000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_06cd5a03d71a4718bfe0f49c9a330b1a"
      unitRef="U002">53215000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_e29f4b9d44ce436ea437fec9ab78796d"
      unitRef="U002">-6993000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_e33ca529121345a8b6ae31a41aa723ed"
      unitRef="U002">165369000</us-gaap:CostsAndExpenses>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_16991713b8214921b9185f73f0b869f0"
      unitRef="U002">33636000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190701to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_c9e381a015c84feda7b3e08764d8e527"
      unitRef="U002">-32591000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190701to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_5638d93992f74ea6b438a00ed72d78ab"
      unitRef="U002">1478000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190701to20190930"
      decimals="-3"
      id="Fact_e3aad9d647ab485387effff6f0747a0d"
      unitRef="U002">2523000</us-gaap:OperatingIncomeLoss>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_2d84e097aaa8452a987ecd7b7ef64e2a"
      unitRef="U002">70010000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_01256613cdd443688f89f70fce4756cb"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_7826ba25f57f45efae65ed71f31bbc24"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_f0ff404e2e044dd59bb2259c1ee7ad05"
      unitRef="U002">70010000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_462efc2471ac4bb49822a87d39cc0d66"
      unitRef="U002">7946000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_531983e7fc1d49468168054ab8840f6b"
      unitRef="U002">12000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_4ef6d1f6d5de421292778c4c210e1e20"
      unitRef="U002">-7200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_e3f771dc08a84be58bf5e2c1550325fe"
      unitRef="U002">12746000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_026f56ce5a3e400089c37d0bb4b394d8"
      unitRef="U002">77956000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_69febac3fe8049899394ef86b27db325"
      unitRef="U002">12000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_76994a2169b444eabba0f3cee2fd4803"
      unitRef="U002">-7200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_3904d9249d67416aa03f65c12b8166c7"
      unitRef="U002">82756000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_19340268b46749d1acf8619fa5ab56d6"
      unitRef="U002">100105000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_86c01d862cc8479e96b53d3416c2a678"
      unitRef="U002">7241000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_197b40371db441b1b8c8a68ad699f009"
      unitRef="U002">-44707000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_d604786849aa4294ade4374fde2c8a36"
      unitRef="U002">62639000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_79b7ff155fa34efab669148836c429d2"
      unitRef="U002">178061000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_8072f6800c3f42d5870ad2f79e40be14"
      unitRef="U002">19241000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_66e13b201ea04fb5aa09953de816359f"
      unitRef="U002">-51907000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_865505e750c449a582f0a048347cce9c"
      unitRef="U002">145395000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:CostsAndExpenses
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_3c4c72c6a09547cfb7c62607e9ce0675"
      unitRef="U002">87664000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_32bbf75a2b3e49a3b8ca531695f8c5e2"
      unitRef="U002">84249000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_fd3a46040b484041ad1788b93720843f"
      unitRef="U002">-7946000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_996549b1efb842bfa681165a11e9c5a3"
      unitRef="U002">163967000</us-gaap:CostsAndExpenses>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_f90eb41ecadf410b914e006c3814712e"
      unitRef="U002">90397000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180701to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_5f8bbdbf1f1845deacc26c5e02dcc7bd"
      unitRef="U002">-65008000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180701to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_7ae6bebdda974d689507d7b8d1557e4d"
      unitRef="U002">-43961000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180701to20180930"
      decimals="-3"
      id="Fact_76ca5e065c58496b9fc4aad4ab5b6b50"
      unitRef="U002">-18572000</us-gaap:OperatingIncomeLoss>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_640fcd24deab492aab126433a9ef8352"
      unitRef="U002">211884000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_0387152e55e74b63af15df208e7a370b"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_9e176794a7b749849a2083f3f1bfef5a"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_7977f9ee2daf4f2c9a39c2838b5553e6"
      unitRef="U002">211884000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_ed4d10d33ef14e4ab59273bf3fb6306c"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ProductMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_c722e9964b5643daa95aebf142f71560"
      unitRef="U002">28563000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_d8acd965f2c7499182c997da7e03ba16"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_69c3c61419bf437eb6eb78ef1954f3d3"
      unitRef="U002">28563000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_9bdaf2f2f59842ddad44e83a56d6b97a"
      unitRef="U002">8466000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_12d23620e6d64f7e9a6665138998e516"
      unitRef="U002">6172000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_8ca0270f0b1d4ff0853035da41cc532f"
      unitRef="U002">-3000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_5eba0150505e4f55ba65e72325562287"
      unitRef="U002">11638000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_14d3ac6051474c57b4044a9e3c25dc5f"
      unitRef="U002">220350000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_157a939271cd4662beddcbbf1f1ffab2"
      unitRef="U002">34735000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_06899842b21349a89885c3510ac18e2a"
      unitRef="U002">-3000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_ceef1111917b4b4a9a57e31726e8a138"
      unitRef="U002">252085000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_364b1bc2ef1f44edbb8d33552c9a6b2e"
      unitRef="U002">294512000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_57078f844c84488597a9c42691c14792"
      unitRef="U002">176328000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_846a00142e7c4fbbb69f8ddddfa1d195"
      unitRef="U002">-94007000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_7455062d26394bb984474d050ef9cb68"
      unitRef="U002">376833000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_466c1123e4fe4ec6987969e0a983142e"
      unitRef="U002">514862000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_516791355aa14815ac8ebd7b1fbaa749"
      unitRef="U002">211063000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_0af4398850084064aa910459b3b4b314"
      unitRef="U002">-97007000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_faaa59c4dce74ab69b467855f90a5daa"
      unitRef="U002">628918000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:CostsAndExpenses
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_2477b75f32d741b690b2159a58975f6c"
      unitRef="U002">355437000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_c00c18f9087a46979e3ec82f85e108f2"
      unitRef="U002">256152000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_e46418be4e0043239214b189774788cd"
      unitRef="U002">-87900000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_af391b005edc467c8376dac5e4c4d1bb"
      unitRef="U002">523689000</us-gaap:CostsAndExpenses>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_7fb6c0d939b847d89e201679f680390b"
      unitRef="U002">159425000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190101to20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_a9d58f5f33084b85a44e3b4857953f89"
      unitRef="U002">-45089000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190101to20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_8e0e875287004df7a4873512ac7d3829"
      unitRef="U002">-9107000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20190101to20190930"
      decimals="-3"
      id="Fact_b062096c1aa14a4c816b2464b77ace26"
      unitRef="U002">105229000</us-gaap:OperatingIncomeLoss>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_04e06da9c3be457b93e3f21714719d0c"
      unitRef="U002">167743000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_fdaaf16de0e241abbe360e67e9872c24"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_324b047595da4acdbf620de786c48c7d"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_SPINRAZARoyaltiesMember"
      decimals="-3"
      id="Fact_7fb1f23159c74407bc90a22aecd4e1f2"
      unitRef="U002">167743000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_2cd414e0a5f246e08e5c16019fc6edd8"
      unitRef="U002">9432000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_b20440321a31424ca56f6e02b58c78b9"
      unitRef="U002">12000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_b6462f0156254f148056dd9585907bab"
      unitRef="U002">-7200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_5a72ada2f2774b4c836d96a696659386"
      unitRef="U002">14232000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_afc55777a60b40b8ab2675e014f4f7f9"
      unitRef="U002">177175000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_CommercialMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_893bcf86d8af4010b8b5b5625efd3825"
      unitRef="U002">12000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_9790328f1cae47cbb22831987fadf1ed"
      unitRef="U002">-7200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_13dfdcb4903d438ab46f02c4643a0e0a"
      unitRef="U002">181975000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_2bf9058c58da475d9caffd1182cb7887"
      unitRef="U002">232850000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_0562374ab6c84fd99338737c88e29283"
      unitRef="U002">42670000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_af31e747523849f79c6fa2575c909c6b"
      unitRef="U002">-49936000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ProductOrServiceAxis_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember"
      decimals="-3"
      id="Fact_37db24a2d53c479db81ad2e54f057dd6"
      unitRef="U002">225584000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_c739d545f46840f0a6054d46e77ca859"
      unitRef="U002">410025000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_4cf45017bd1e45ea9b5a64d162bb6904"
      unitRef="U002">54670000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_3b0ded8164864ba88a14929cdf2f382f"
      unitRef="U002">-57136000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_ded482ce48c4445794a4185228731868"
      unitRef="U002">407559000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:CostsAndExpenses
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_2d96460f21d94905a83624cb023a3c3f"
      unitRef="U002">279084000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_805b13df07d94a4b94d66ee7e338e924"
      unitRef="U002">213428000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_98ce477691184e1b960a1fea451e4560"
      unitRef="U002">-12796000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_5a9a86233bf44c7b99d0d2473f15fa8f"
      unitRef="U002">479716000</us-gaap:CostsAndExpenses>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_20a20d1c63f240609a8add7169741e07"
      unitRef="U002">130941000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180101to20180930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_24e4ceca8f6c403e887f6e1c0a9ea9c4"
      unitRef="U002">-158758000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180101to20180930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_cd9ab2269af44131898565bf9139fcc7"
      unitRef="U002">-44340000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20180101to20180930"
      decimals="-3"
      id="Fact_75f9aed8281f40488f8b98dfb0b42f91"
      unitRef="U002">-72157000</us-gaap:OperatingIncomeLoss>
    <us-gaap:Assets
      contextRef="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_c3a5810a7f784135902bba47ba0b155d"
      unitRef="U002">3233175000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20190930_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_fa83731928db429989893cb80f73b1d6"
      unitRef="U002">383167000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20190930_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_873771d081084385a5b4d5d09eaf5746"
      unitRef="U002">-721353000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20190930"
      decimals="-3"
      id="Fact_4208e1cc956a42b5920991c0c42909bd"
      unitRef="U002">2894989000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_IonisCoreMember"
      decimals="-3"
      id="Fact_ab44db8a535a4a40ae1895ff99b64614"
      unitRef="U002">2975491000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20181231_ConsolidationItemsAxis_OperatingSegmentsMember_StatementBusinessSegmentsAxis_AkceaTherapeuticsMember"
      decimals="-3"
      id="Fact_efaf7ebcb4eb4b7da50d13fc3b7ed6b1"
      unitRef="U002">365261000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20181231_ConsolidationItemsAxis_IntersegmentEliminationMember"
      decimals="-3"
      id="Fact_acec55974f0141ff85cd77b37d1732d8"
      unitRef="U002">-672968000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20181231"
      decimals="-3"
      id="Fact_270e73cd1d254acf8d16d0b0155bd3e8"
      unitRef="U002">2667784000</us-gaap:Assets>
    <link:footnoteLink
      xlink:role="http://www.xbrl.org/2003/role/link"
      xlink:type="extended">
        <link:loc
          xlink:href="#Fact_138aaf4a47a148d091cceb4ced2e1cfc"
          xlink:label="Fact_138aaf4a47a148d091cceb4ced2e1cfc"
          xlink:type="locator"/>
        <link:footnote id="Foot_305e1d6b0b66460686148b2ce6e01d9b" xlink:label="Foot_305e1d6b0b66460686148b2ce6e01d9b" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Our available-for-sale securities are held at amortized cost.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_138aaf4a47a148d091cceb4ced2e1cfc"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_ea15651e08bd4b8b990074a9aa80683d"
          xlink:label="Fact_ea15651e08bd4b8b990074a9aa80683d"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_ea15651e08bd4b8b990074a9aa80683d"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_206242051e2c4d94b28d4e87712895a7"
          xlink:label="Fact_206242051e2c4d94b28d4e87712895a7"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_206242051e2c4d94b28d4e87712895a7"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_f4c2236cedf849b8971016981b4f39e6"
          xlink:label="Fact_f4c2236cedf849b8971016981b4f39e6"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_f4c2236cedf849b8971016981b4f39e6"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_bed56c4d2fcd4a74a0a1ccb2d57c9639"
          xlink:label="Fact_bed56c4d2fcd4a74a0a1ccb2d57c9639"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_bed56c4d2fcd4a74a0a1ccb2d57c9639"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_9801fd693cf84c299d17cb204de46d5f"
          xlink:label="Fact_9801fd693cf84c299d17cb204de46d5f"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_9801fd693cf84c299d17cb204de46d5f"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_248f6769580b4861a0b529d0816594e0"
          xlink:label="Fact_248f6769580b4861a0b529d0816594e0"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_248f6769580b4861a0b529d0816594e0"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_78a409a549ef459db614b179f7ae1230"
          xlink:label="Fact_78a409a549ef459db614b179f7ae1230"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_78a409a549ef459db614b179f7ae1230"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_f4ce593384ef4b7d83aad4901d4548b6"
          xlink:label="Fact_f4ce593384ef4b7d83aad4901d4548b6"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_f4ce593384ef4b7d83aad4901d4548b6"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_80f9e07c881d4103821ad1c51c0e34b7"
          xlink:label="Fact_80f9e07c881d4103821ad1c51c0e34b7"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_80f9e07c881d4103821ad1c51c0e34b7"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_0187b54b654f4e109666c7737fc2551d"
          xlink:label="Fact_0187b54b654f4e109666c7737fc2551d"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_0187b54b654f4e109666c7737fc2551d"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_9015169599984f5a9691efcc7214ed32"
          xlink:label="Fact_9015169599984f5a9691efcc7214ed32"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_9015169599984f5a9691efcc7214ed32"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_15869a0e101243b38f48dfa9071509af"
          xlink:label="Fact_15869a0e101243b38f48dfa9071509af"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_15869a0e101243b38f48dfa9071509af"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_cb912863d431429d957f3c945ccb7b83"
          xlink:label="Fact_cb912863d431429d957f3c945ccb7b83"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_cb912863d431429d957f3c945ccb7b83"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_5bd44b202ba0488e976f0c108e51d72a"
          xlink:label="Fact_5bd44b202ba0488e976f0c108e51d72a"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_5bd44b202ba0488e976f0c108e51d72a"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_9339c651e1c64d02a58d7ef8f3a401fa"
          xlink:label="Fact_9339c651e1c64d02a58d7ef8f3a401fa"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_9339c651e1c64d02a58d7ef8f3a401fa"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_eab544f46afa456189480b40679240a9"
          xlink:label="Fact_eab544f46afa456189480b40679240a9"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_eab544f46afa456189480b40679240a9"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_2536445b56a5427d99424937cbc97ea6"
          xlink:label="Fact_2536445b56a5427d99424937cbc97ea6"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_2536445b56a5427d99424937cbc97ea6"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_1c044e91f5e742a3961b4f59ca6ef285"
          xlink:label="Fact_1c044e91f5e742a3961b4f59ca6ef285"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_1c044e91f5e742a3961b4f59ca6ef285"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_1f3e39cc38284f8aad73189eea7bbf14"
          xlink:label="Fact_1f3e39cc38284f8aad73189eea7bbf14"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_1f3e39cc38284f8aad73189eea7bbf14"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_9f527800450b4ccfad702bd8b0ced078"
          xlink:label="Fact_9f527800450b4ccfad702bd8b0ced078"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_9f527800450b4ccfad702bd8b0ced078"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_b181ed8da53647f8a6b292342a235f93"
          xlink:label="Fact_b181ed8da53647f8a6b292342a235f93"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_b181ed8da53647f8a6b292342a235f93"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_a40f4d8491b24020962dbd41df0b3f94"
          xlink:label="Fact_a40f4d8491b24020962dbd41df0b3f94"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_a40f4d8491b24020962dbd41df0b3f94"
          xlink:to="Foot_305e1d6b0b66460686148b2ce6e01d9b"
          xlink:type="arc"/>
        <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_5bd44b202ba0488e976f0c108e51d72a"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_1c044e91f5e742a3961b4f59ca6ef285"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_1f3e39cc38284f8aad73189eea7bbf14"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_005ea5438f1a425e8a7d2f6ca3f789f8"
          xlink:label="Fact_005ea5438f1a425e8a7d2f6ca3f789f8"
          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">$16.6 million was included in cash and cash equivalents, with the difference included in short-term investments.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_005ea5438f1a425e8a7d2f6ca3f789f8"
          xlink:to="Foot_f8be77aa66f84482abc56f1b540c3aca"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_26191d5384f64272905581a8fe8b850e"
          xlink:label="Fact_26191d5384f64272905581a8fe8b850e"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_26191d5384f64272905581a8fe8b850e"
          xlink:to="Foot_f8be77aa66f84482abc56f1b540c3aca"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_d2cf55f51c9147beb6d1c06acf8ed2dc"
          xlink:label="Fact_d2cf55f51c9147beb6d1c06acf8ed2dc"
          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">$50.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_d2cf55f51c9147beb6d1c06acf8ed2dc"
          xlink:to="Foot_2009e9e101cd4940acd892bb1ca9a15f"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_31607d0464414d63a9d40c3bda86cebd"
          xlink:label="Fact_31607d0464414d63a9d40c3bda86cebd"
          xlink:type="locator"/>
        <link:footnote id="Foot_e555e136aa274c8e882586614fcdf5b2" xlink:label="Foot_e555e136aa274c8e882586614fcdf5b2" 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_31607d0464414d63a9d40c3bda86cebd"
          xlink:to="Foot_e555e136aa274c8e882586614fcdf5b2"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_cf2cd8ea24c34a298b35a62e5c63fe49"
          xlink:label="Fact_cf2cd8ea24c34a298b35a62e5c63fe49"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_cf2cd8ea24c34a298b35a62e5c63fe49"
          xlink:to="Foot_e555e136aa274c8e882586614fcdf5b2"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_719745a58a2745968c9eec989ba98101"
          xlink:label="Fact_719745a58a2745968c9eec989ba98101"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_719745a58a2745968c9eec989ba98101"
          xlink:to="Foot_e555e136aa274c8e882586614fcdf5b2"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_303ee7acffb64b30b37958792583e02d"
          xlink:label="Fact_303ee7acffb64b30b37958792583e02d"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_303ee7acffb64b30b37958792583e02d"
          xlink:to="Foot_e555e136aa274c8e882586614fcdf5b2"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_d28150ca7b45448fa25fbb6cd2de43d0"
          xlink:label="Fact_d28150ca7b45448fa25fbb6cd2de43d0"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_d28150ca7b45448fa25fbb6cd2de43d0"
          xlink:to="Foot_e555e136aa274c8e882586614fcdf5b2"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_7e9a01d143344a90abd0d3c282087ea8"
          xlink:label="Fact_7e9a01d143344a90abd0d3c282087ea8"
          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">$3.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_7e9a01d143344a90abd0d3c282087ea8"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_6e8ff7ac339a47ee87988299df92fe42"
          xlink:label="Fact_6e8ff7ac339a47ee87988299df92fe42"
          xlink:type="locator"/>
        <link:footnote id="Foot_f21495f28c8740a99946dade31b02bd8" xlink:label="Foot_f21495f28c8740a99946dade31b02bd8" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$14.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_6e8ff7ac339a47ee87988299df92fe42"
          xlink:to="Foot_f21495f28c8740a99946dade31b02bd8"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_57ccf9920b8146f388ce592d258d1e8f"
          xlink:label="Fact_57ccf9920b8146f388ce592d258d1e8f"
          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.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_57ccf9920b8146f388ce592d258d1e8f"
          xlink:to="Foot_a07f61350d6c43dcbc95f9a5735b974a"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_3e8681d673cb4651bd1fa1b44eaab381"
          xlink:label="Fact_3e8681d673cb4651bd1fa1b44eaab381"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_3e8681d673cb4651bd1fa1b44eaab381"
          xlink:to="Foot_a07f61350d6c43dcbc95f9a5735b974a"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_1f42a3296a8a46159ca5daccd95f28b8"
          xlink:label="Fact_1f42a3296a8a46159ca5daccd95f28b8"
          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">We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our condensed consolidated balance sheet.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_1f42a3296a8a46159ca5daccd95f28b8"
          xlink:to="Foot_20cf8a92586d4d88bc45b040cb662025"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_8433f3b9512246ac8207c5a05c776b60"
          xlink:label="Fact_8433f3b9512246ac8207c5a05c776b60"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_8433f3b9512246ac8207c5a05c776b60"
          xlink:to="Foot_20cf8a92586d4d88bc45b040cb662025"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_48764182e11a4bb5958ad2aaafc3c0c6"
          xlink:label="Fact_48764182e11a4bb5958ad2aaafc3c0c6"
          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">Included in other current assets.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_48764182e11a4bb5958ad2aaafc3c0c6"
          xlink:to="Foot_f0cb78a83b31476988ccfd169edddb78"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_df377b1e9061452b8f3d582001e6a515"
          xlink:label="Fact_df377b1e9061452b8f3d582001e6a515"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_df377b1e9061452b8f3d582001e6a515"
          xlink:to="Foot_f0cb78a83b31476988ccfd169edddb78"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_3068d59045b74301b2c28fc3dfb6b8be"
          xlink:label="Fact_3068d59045b74301b2c28fc3dfb6b8be"
          xlink:type="locator"/>
        <link:footnote id="Foot_550ffd62f7c940f1b6c1073473427cdb" xlink:label="Foot_550ffd62f7c940f1b6c1073473427cdb" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Included in deposits and other assets on our condensed consolidated balance sheet.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_3068d59045b74301b2c28fc3dfb6b8be"
          xlink:to="Foot_550ffd62f7c940f1b6c1073473427cdb"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_fbe5ecbb80b44b659c35900b4d87399c"
          xlink:label="Fact_fbe5ecbb80b44b659c35900b4d87399c"
          xlink:type="locator"/>
        <link:footnote id="Foot_f913e9fa94634b87a1ff2c11bfad2e80" xlink:label="Foot_f913e9fa94634b87a1ff2c11bfad2e80" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_fbe5ecbb80b44b659c35900b4d87399c"
          xlink:to="Foot_f913e9fa94634b87a1ff2c11bfad2e80"
          xlink:type="arc"/>
    </link:footnoteLink>
</xbrl>
</XML>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>56
<FILENAME>R33.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6828320592">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="nump">$ 0.19<span></span>
</td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="nump">$ 0.81<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 26,163<span></span>
</td>
<td class="num">$ (4,559)<span></span>
</td>
<td class="nump">$ 109,730<span></span>
</td>
<td class="num">$ (46,335)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Net income (loss) available to Ionis common shareholders</a></td>
<td class="nump">$ 26,158<span></span>
</td>
<td class="num">$ (4,617)<span></span>
</td>
<td class="nump">$ 112,764<span></span>
</td>
<td class="num">$ (43,163)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Weighted average shares outstanding (in shares)</a></td>
<td class="nump">140,551<span></span>
</td>
<td class="nump">137,346<span></span>
</td>
<td class="nump">139,800<span></span>
</td>
<td class="nump">130,507<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted', window );">Income available to Ionis common shareholders</a></td>
<td class="nump">$ 26,158<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 112,764<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan', window );">Shares issuable related to our Employee Stock Purchase Plan (in shares)</a></td>
<td class="nump">20<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income per share (in shares)</a></td>
<td class="nump">143,408<span></span>
</td>
<td class="nump">137,346<span></span>
</td>
<td class="nump">142,821<span></span>
</td>
<td class="nump">130,507<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income per share (in dollars per share)</a></td>
<td class="nump">$ 0.18<span></span>
</td>
<td class="num">$ (0.03)<span></span>
</td>
<td class="nump">$ 0.79<span></span>
</td>
<td class="num">$ (0.33)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="nump">1,993<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,208<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockMember', window );">Restricted Stock Awards [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="nump">844<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">793<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember', window );">Ionis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 49,930<span></span>
</td>
<td class="nump">$ 43,226<span></span>
</td>
<td class="nump">$ 140,938<span></span>
</td>
<td class="nump">$ 67,517<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="num">$ (23,772)<span></span>
</td>
<td class="num">$ (47,843)<span></span>
</td>
<td class="num">$ (28,174)<span></span>
</td>
<td class="num">$ (110,680)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member] | Common Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="nump">70,221<span></span>
</td>
<td class="nump">65,538<span></span>
</td>
<td class="nump">69,681<span></span>
</td>
<td class="nump">57,347<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="num">$ (0.34)<span></span>
</td>
<td class="num">$ (0.73)<span></span>
</td>
<td class="num">$ (0.40)<span></span>
</td>
<td class="num">$ (1.93)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net income (loss)</a></td>
<td class="num">$ (23,772)<span></span>
</td>
<td class="num">$ (47,843)<span></span>
</td>
<td class="num">$ (28,174)<span></span>
</td>
<td class="num">$ (110,680)<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_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_WeightedAverageNumberOfSharesOwnedInSubsidiary</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637232&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 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1337-109256<br><br>Reference 3: 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=117327953&amp;loc=d3e4984-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<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> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<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 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1252-109256<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637391&amp;loc=SL114874048-224260<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=SL5780133-109256<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_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasicAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasicAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=117327953&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 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1252-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><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(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637391&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 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1337-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(21))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<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=117326831&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 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(19))<br> -URI http://asc.fasb.org/extlink&amp;oid=116637232&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_EarningsPerShareDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of share based payment arrangements using the treasury stock method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28A<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1500-109256<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 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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=116637391&amp;loc=SL114874048-224260<br><br>Reference 3: 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=118930883&amp;loc=SL7669625-108580<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=116637232&amp;loc=SL114874131-224263<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 S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=116634182&amp;loc=SL114868664-224227<br><br>Reference 6: 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=118932676&amp;loc=d3e3602-108585<br><br>Reference 7: 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> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=109234566&amp;loc=d3e22694-107794<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 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1377-109256<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_NetIncomeLossAvailableToCommonStockholdersBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities, and addition from assumption of issuance of common shares for dilutive potential common shares; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<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=117326831&amp;loc=d3e1505-109256<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 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&amp;loc=d3e1377-109256<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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://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 (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=117326831&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://fasb.org/us-gaap/role/ref/legacyRef<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=117326831&amp;loc=d3e1448-109256<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 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6371337&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_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_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_AwardTypeAxis=us-gaap_RestrictedStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( 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_RestrictedStockMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementClassOfStockAxis=us-gaap_CommonStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementClassOfStockAxis=us-gaap_CommonStockMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>57
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6971173040">
<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">9 Months Ended</th>
</tr>
<tr><th class="th">
<div>Sep. 30, 2019 </div>
<div>Company</div>
</th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract', window );"><strong>Contract Maturity of Available-for-Sale Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage', window );">One year or less</a></td>
<td class="nump">69.00%<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">22.00%<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_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage', window );">After two years but within three years</a></td>
<td class="nump">9.00%<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage', window );">Total</a></td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage', window );">Percentage of available-for-sale securities with a maturity of less than two years</a></td>
<td class="nump">91.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange1', window );">Maximum contract maturity period, range 1</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange2', window );">Maximum contract maturity period, range 2</a></td>
<td class="text">2 years<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange3', window );">Maximum contract maturity period, range 3</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_invest_InvestmentsScheduleAbstract', window );"><strong>Ownership Interests in Private and Public Companies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly-held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">2<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_invest_InvestmentsScheduleAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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;">invest_InvestmentsScheduleAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>invest_</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_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 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_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange3</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
</tr>
<tr>
<td style="padding-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>58
<FILENAME>FilingSummary.xml
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<XML>
<?xml version='1.0' encoding='utf-8'?>
<FilingSummary>
  <Version>3.19.3</Version>
  <ProcessingTime/>
  <ReportFormat>html</ReportFormat>
  <ContextCount>392</ContextCount>
  <ElementCount>348</ElementCount>
  <EntityCount>1</EntityCount>
  <FootnotesReported>true</FootnotesReported>
  <SegmentCount>77</SegmentCount>
  <ScenarioCount>0</ScenarioCount>
  <TuplesReported>false</TuplesReported>
  <UnitCount>15</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://isispharm.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 (Unaudited)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnaudited</Role>
      <ShortName>CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited)</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 (Unaudited) (Parenthetical)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical</Role>
      <ShortName>CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited) (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 (Unaudited)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CondensedConsolidatedStatementsOfOperationsUnaudited</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited)</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 INCOME (LOSS) (Unaudited)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CondensedConsolidatedStatementsOfComprehensiveIncomeLossUnaudited</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Unaudited)</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 (Unaudited)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CondensedConsolidatedStatementsOfStockholdersEquityUnaudited</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY (Unaudited)</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 (Unaudited)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CondensedConsolidatedStatementsOfCashFlowsUnaudited</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited)</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://isispharm.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://isispharm.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://isispharm.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://isispharm.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 - Operating Leases</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/OperatingLeases</Role>
      <ShortName>Operating Leases</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 - Income Taxes</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/IncomeTaxes</Role>
      <ShortName>Income Taxes</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 - Collaborative Arrangements and Licensing Agreements</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>14</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R15.htm</HtmlFileName>
      <LongName>060800 - Disclosure - Segment Information</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SegmentInformation</Role>
      <ShortName>Segment Information</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>15</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R16.htm</HtmlFileName>
      <LongName>070100 - Disclosure - Basis of Presentation (Policies)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/BasisOfPresentationPolicies</Role>
      <ShortName>Basis of Presentation (Policies)</ShortName>
      <MenuCategory>Policies</MenuCategory>
      <ParentRole>http://isispharm.com/role/SignificantAccountingPolicies</ParentRole>
      <Position>16</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R17.htm</HtmlFileName>
      <LongName>070200 - Disclosure - Significant Accounting Policies (Policies)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesPolicies</Role>
      <ShortName>Significant Accounting Policies (Policies)</ShortName>
      <MenuCategory>Policies</MenuCategory>
      <ParentRole>http://isispharm.com/role/SignificantAccountingPolicies</ParentRole>
      <Position>17</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R18.htm</HtmlFileName>
      <LongName>080200 - Disclosure - Significant Accounting Policies (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesTables</Role>
      <ShortName>Significant Accounting Policies (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://isispharm.com/role/SignificantAccountingPolicies</ParentRole>
      <Position>18</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R19.htm</HtmlFileName>
      <LongName>080300 - Disclosure - Investments (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/InvestmentsTables</Role>
      <ShortName>Investments (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://isispharm.com/role/Investments</ParentRole>
      <Position>19</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R20.htm</HtmlFileName>
      <LongName>080400 - Disclosure - Fair Value Measurements (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/FairValueMeasurementsTables</Role>
      <ShortName>Fair Value Measurements (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://isispharm.com/role/FairValueMeasurements</ParentRole>
      <Position>20</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R21.htm</HtmlFileName>
      <LongName>080500 - Disclosure - Operating Leases (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/OperatingLeasesTables</Role>
      <ShortName>Operating Leases (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://isispharm.com/role/OperatingLeases</ParentRole>
      <Position>21</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R22.htm</HtmlFileName>
      <LongName>080700 - Disclosure - Collaborative Arrangements and Licensing Agreements (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreements</ParentRole>
      <Position>22</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R23.htm</HtmlFileName>
      <LongName>080800 - Disclosure - Segment Information (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SegmentInformationTables</Role>
      <ShortName>Segment Information (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://isispharm.com/role/SegmentInformation</ParentRole>
      <Position>23</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R24.htm</HtmlFileName>
      <LongName>090100 - Disclosure - Basis of Presentation (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/BasisOfPresentationDetails</Role>
      <ShortName>Basis of Presentation (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/BasisOfPresentationPolicies</ParentRole>
      <Position>24</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R25.htm</HtmlFileName>
      <LongName>090200 - Disclosure - Significant Accounting Policies, Revenue Recognition (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails</Role>
      <ShortName>Significant Accounting Policies, Revenue Recognition (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>25</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R26.htm</HtmlFileName>
      <LongName>090202 - Disclosure - Significant Accounting Policies, Contracts Receivable (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesContractsReceivableDetails</Role>
      <ShortName>Significant Accounting Policies, Contracts Receivable (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>26</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R27.htm</HtmlFileName>
      <LongName>090204 - Disclosure - Significant Accounting Policies, Deferred Revenue (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesDeferredRevenueDetails</Role>
      <ShortName>Significant Accounting Policies, Deferred Revenue (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>27</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R28.htm</HtmlFileName>
      <LongName>090206 - Disclosure - Significant Accounting Policies, Cost of Products Sold (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesCostOfProductsSoldDetails</Role>
      <ShortName>Significant Accounting Policies, Cost of Products Sold (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>28</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R29.htm</HtmlFileName>
      <LongName>090208 - Disclosure - Significant Accounting Policies, Noncontrolling Interest in Akcea (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesNoncontrollingInterestInAkceaDetails</Role>
      <ShortName>Significant Accounting Policies, Noncontrolling Interest in Akcea (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>29</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R30.htm</HtmlFileName>
      <LongName>090210 - Disclosure - Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails</Role>
      <ShortName>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>30</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R31.htm</HtmlFileName>
      <LongName>090212 - Disclosure - Significant Accounting Policies, Inventory Valuation (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesInventoryValuationDetails</Role>
      <ShortName>Significant Accounting Policies, Inventory Valuation (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>31</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R32.htm</HtmlFileName>
      <LongName>090214 - Disclosure - Significant Accounting Policies, Leases (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesLeasesDetails</Role>
      <ShortName>Significant Accounting Policies, Leases (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>32</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R33.htm</HtmlFileName>
      <LongName>090216 - Disclosure - Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesBasicAndDilutedNetIncomeLossPerShareDetails</Role>
      <ShortName>Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>33</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R34.htm</HtmlFileName>
      <LongName>090218 - Disclosure - Significant Accounting Policies, Segment Information (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesSegmentInformationDetails</Role>
      <ShortName>Significant Accounting Policies, Segment Information (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>34</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R35.htm</HtmlFileName>
      <LongName>090220 - Disclosure - Significant Accounting Policies, Stock-Based Compensation Expense (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails</Role>
      <ShortName>Significant Accounting Policies, Stock-Based Compensation Expense (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>35</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R36.htm</HtmlFileName>
      <LongName>090222 - Disclosure - Significant Accounting Policies, Share Repurchase Program (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SignificantAccountingPoliciesShareRepurchaseProgramDetails</Role>
      <ShortName>Significant Accounting Policies, Share Repurchase Program (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>36</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R37.htm</HtmlFileName>
      <LongName>090300 - Disclosure - Investments, Contract Maturity of Available-for-Sale Securities (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails</Role>
      <ShortName>Investments, Contract Maturity of Available-for-Sale Securities (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>37</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R38.htm</HtmlFileName>
      <LongName>090302 - Disclosure - Investments, Summary of Investments (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/InvestmentsSummaryOfInvestmentsDetails</Role>
      <ShortName>Investments, Summary of Investments (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>38</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R39.htm</HtmlFileName>
      <LongName>090304 - Disclosure - Investments, Investments Temporarily Impaired (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails</Role>
      <ShortName>Investments, Investments Temporarily Impaired (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>39</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R40.htm</HtmlFileName>
      <LongName>090400 - Disclosure - Fair Value Measurements (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/FairValueMeasurementsDetails</Role>
      <ShortName>Fair Value Measurements (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/FairValueMeasurementsTables</ParentRole>
      <Position>40</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R41.htm</HtmlFileName>
      <LongName>090500 - Disclosure - Operating Leases (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/OperatingLeasesDetails</Role>
      <ShortName>Operating Leases (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/OperatingLeasesTables</ParentRole>
      <Position>41</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R42.htm</HtmlFileName>
      <LongName>090600 - Disclosure - Income Taxes (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/IncomeTaxesDetails</Role>
      <ShortName>Income Taxes (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/IncomeTaxes</ParentRole>
      <Position>42</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R43.htm</HtmlFileName>
      <LongName>090700 - Disclosure - Collaborative Arrangements and Licensing Agreements, Biogen (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBiogenDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements, Biogen (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>43</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R44.htm</HtmlFileName>
      <LongName>090706 - Disclosure - Collaborative Arrangements and Licensing Agreements, Bayer (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsBayerDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements, Bayer (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>44</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R45.htm</HtmlFileName>
      <LongName>090708 - Disclosure - Collaborative Arrangements and Licensing Agreements, GSK (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsGskDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements, GSK (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>45</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R46.htm</HtmlFileName>
      <LongName>090710 - Disclosure - Collaborative Arrangements and Licensing Agreements, Roche (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsRocheDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements, Roche (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>46</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R47.htm</HtmlFileName>
      <LongName>090712 - Disclosure - Collaborative Arrangements and Licensing Agreements, Novartis (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsNovartisDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements, Novartis (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>47</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R48.htm</HtmlFileName>
      <LongName>090716 - Disclosure - Collaborative Arrangements and Licensing Agreements, Pfizer (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsPfizerDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements, Pfizer (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>48</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R49.htm</HtmlFileName>
      <LongName>090800 - Disclosure - Segment Information (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://isispharm.com/role/SegmentInformationDetails</Role>
      <ShortName>Segment Information (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://isispharm.com/role/SegmentInformationTables</ParentRole>
      <Position>49</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>ex10_2.htm</File>
    <File>ex10_3.htm</File>
    <File>ex31_1.htm</File>
    <File>ex31_2.htm</File>
    <File>ex32_1.htm</File>
    <File>ions-20190930.xsd</File>
    <File>ions-20190930_cal.xml</File>
    <File>ions-20190930_def.xml</File>
    <File>ions-20190930_lab.xml</File>
    <File>ions-20190930_pre.xml</File>
  </InputFiles>
  <SupplementalFiles/>
  <BaseTaxonomies>
    <BaseTaxonomy>http://fasb.org/srt/2019-01-31</BaseTaxonomy>
    <BaseTaxonomy>http://xbrl.sec.gov/dei/2019-01-31</BaseTaxonomy>
    <BaseTaxonomy>http://xbrl.sec.gov/invest/2013-01-31</BaseTaxonomy>
    <BaseTaxonomy>http://fasb.org/us-gaap/2019-01-31</BaseTaxonomy>
  </BaseTaxonomies>
  <HasPresentationLinkbase>true</HasPresentationLinkbase>
  <HasCalculationLinkbase>true</HasCalculationLinkbase>
</FilingSummary>
</XML>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>59
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6637112416">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) (Unaudited) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="nump">$ 18,432<span></span>
</td>
<td class="num">$ (20,365)<span></span>
</td>
<td class="nump">$ 99,304<span></span>
</td>
<td class="num">$ (87,747)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized gains (losses) on debt securities, net of tax</a></td>
<td class="num">(1,110)<span></span>
</td>
<td class="nump">133<span></span>
</td>
<td class="nump">6,666<span></span>
</td>
<td class="num">(834)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Currency translation adjustment</a></td>
<td class="num">(13)<span></span>
</td>
<td class="num">(31)<span></span>
</td>
<td class="num">(25)<span></span>
</td>
<td class="nump">61<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest', window );">Comprehensive income (loss)</a></td>
<td class="nump">17,309<span></span>
</td>
<td class="num">(20,263)<span></span>
</td>
<td class="nump">105,945<span></span>
</td>
<td class="num">(88,520)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest', window );">Comprehensive loss attributable to noncontrolling interests</a></td>
<td class="num">(7,729)<span></span>
</td>
<td class="num">(13,943)<span></span>
</td>
<td class="num">(10,423)<span></span>
</td>
<td class="num">(38,005)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive income (loss) attributable to Ionis Pharmaceuticals, Inc. stockholders</a></td>
<td class="nump">$ 25,038<span></span>
</td>
<td class="num">$ (6,320)<span></span>
</td>
<td class="nump">$ 116,368<span></span>
</td>
<td class="num">$ (50,515)<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://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=118930883&amp;loc=d3e557-108580<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 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<br><br>Reference 3: 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=118930883&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_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 (loss) and other comprehensive income (loss), attributable to noncontrolling interests. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591552-111686<br><br>Reference 3: 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=118930883&amp;loc=SL7669619-108580<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 21<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4613674-111683<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591552-111686<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<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 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<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_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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://fasb.org/us-gaap/role/ref/legacyRef<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 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32157-110900<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<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 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 10A<br> -Subparagraph (a-c)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669646-108580<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 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&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, before reclassification adjustments, of unrealized holding gain (loss) on available-for-sale securities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><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=118930883&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=118930883&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669619-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118930883&amp;loc=SL7669625-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<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=115929826&amp;loc=d3e8736-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591551-111686<br><br>Reference 7: 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 2<br> -URI http://asc.fasb.org/extlink&amp;oid=118932676&amp;loc=d3e3000-108585<br><br>Reference 8: 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 19<br> -URI http://asc.fasb.org/extlink&amp;oid=108774443&amp;loc=SL4569616-111683<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI http://asc.fasb.org/extlink&amp;oid=116874947&amp;loc=SL4591552-111686<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>60
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6815633712">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureTextBlock', window );">Segment Information</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Segment Information</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> reportable segments, Ionis Core and Akcea Therapeutics. </span>At September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>we owned approximately 75 percent of Akcea.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class medicines for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Akcea is </span>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Akcea generates revenue from TEGSEDI and WAYLIVRA product sales and from its collaborations.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables show our segment revenue and income (loss) from operations for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands), respectively.</div>

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

<table cellpadding="0" cellspacing="0" id="z0ad30f1f4f2a4ba8890de9668d5998f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81,672</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81,672</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,945</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,945</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">136</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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;">2,082</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83,618</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,081</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,699</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,165</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,543</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,515</div></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;">72,193</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">152,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,624</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,515</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,892</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">119,147</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">53,215</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,993</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">165,369</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,636</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,591</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,478</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,523</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="z1fe532a6dd9c40528713d7c7fce08810" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended September 30, 2018</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;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,010</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,010</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,746</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,956</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></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;">82,756</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,105</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,241</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,639</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,061</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">19,241</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(51,907</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">145,395</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87,664</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84,249</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">163,967</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">90,397</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(65,008</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43,961</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(18,572</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="zc3a76d4662b34f2ea78dc5e6136dfb77" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,884</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,884</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,466</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;">6,172</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,638</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">220,350</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,735</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252,085</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">294,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,328</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(94,007</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">376,833</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">514,862</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,063</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(97,007</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">628,918</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">355,437</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">256,152</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(87,900</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">523,689</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159,425</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(45,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,107</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,229</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="zcf2b13dc1bb64910b74499773f3efba3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended September 30, 2018</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;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,743</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,743</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,432</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,232</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">177,175</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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></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;">181,975</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">232,850</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42,670</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(49,936</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">225,584</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">410,025</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,670</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(57,136</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">407,559</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">279,084</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">213,428</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(12,796</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479,716</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,941</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(158,758</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,340</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(72,157</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table shows our total assets by segment at September 30, 2019 and December 31, 2018 (in thousands), respectively.</div>

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

<table cellpadding="0" cellspacing="0" id="z6c5c599a255e4059847439344a157872" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Assets</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;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">September 30, 2019</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,233,175</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">383,167</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(721,353</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2,894,989</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,975,491</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">365,261</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(672,968</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,667,784</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<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_SegmentReportingAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingAbstract</td>
</tr>
<tr>
<td style="padding-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_SegmentReportingDisclosureTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 reporting segments including data and tables. Reportable segments include those that meet any of the following quantitative thresholds a) it's reported revenue, including sales to external customers and intersegment sales or transfers is 10 percent or more of the combined revenue, internal and external, of all operating segments b) the absolute amount of its reported profit or loss is 10 percent or more of the greater, in absolute amount of 1) the combined reported profit of all operating segments that did not report a loss or 2) the combined reported loss of all operating segments that did report a loss c) its assets are 10 percent or more of the combined assets of all operating segments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -URI http://asc.fasb.org/topic&amp;trid=2134510<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingDisclosureTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>61
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6815633712">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 the majority 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that we regularly measure and carry at fair value. At </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>our ProQR investment was <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">subject to trading restrictions that extend to the fourth quarter of 2019; as a result, we</span> included a lack of marketability discount in valuing this investment, which is a Level 3 input.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> The amount we owned in ProQR did not change from </span>December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The tables below segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</span></div>

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

<table cellpadding="0" cellspacing="0" id="ze035bc9b78a548a8a5fdecd96869b42a" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30, 2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">202,904</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">202,904</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,296,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,296,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">283,365</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">283,365</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366,272</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366,272</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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 (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;">43,265</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">43,265</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-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></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div><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%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (5)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: 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: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,195,958</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">569,176</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,626,176</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="z210039b332e745bb8548fc2512c58d45" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146,281</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">146,281</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (6)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,252,960</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,252,960</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">276,612</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">276,612</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">260,154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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 (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;">79,942</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">79,942</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-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></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (5)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,017,298</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">406,435</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,609,514</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines on our condensed consolidated balance sheet:</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zbee9abbccdd54e73807b84f4e3b2b782" 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.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z438bdc6881aa4cb99b165b8919727dda" 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;">$16.6 million was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4a15bc1d737a430282eea21dc5b0bfb3" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z3864b9dae47f4db89495ac682873943c" 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;">$3.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb45245eabfe741ed8a9fa3ca3dc821f5" 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;">Included in other current assets.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd2f62bfc179a4c6ea80ab9be8baa40fe" 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;">$50.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z28e1624d992e41cbb67711b300f91fbe" 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;">$14.2 million was included in cash and cash equivalents, with the difference included in short-term investments.</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 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 1 percent notes had a fair value of $783.7 million at September 30, 2019. 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=117815213&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>62
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6826839232">
<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">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Oct. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_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 " 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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityInteractiveDataCurrent', window );">Entity Interactive Data Current</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityShellCompany', window );">Entity Shell Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntitySmallBusiness', window );">Entity Small Business</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">140,663,254<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_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 " 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 " 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">Sep. 30,  2019<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2019<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">Q3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_DocumentQuarterlyReport', window );">Document Quarterly Report</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_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="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_Security12bTitle', window );">Title of 12(b) Security</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AmendmentFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CityAreaCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CityAreaCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CurrentFiscalYearEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>End date of current fiscal year in the format --MM-DD.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CurrentFiscalYearEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gMonthDayItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalPeriodFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fiscal period values are FY, Q1, Q2, and Q3.  1st, 2nd and 3rd quarter 10-Q or 10-QT statements have value Q1, Q2, and Q3 respectively, with 10-K, 10-KT or other fiscal year statements having FY.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalPeriodFocus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fiscalPeriodItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalYearFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal year of the document report in CCYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalYearFocus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gYearItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentPeriodEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The end date of the period reflected on the cover page if a periodic report. For all other reports and registration statements containing historical data, it is the date up through which that historical data is presented.  If there is no historical data in the report, use the filing date. The format of the date is CCYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentPeriodEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentQuarterlyReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as an quarterly report.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-Q<br> -Number 240<br> -Section 13<br> -Subsection a-13<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentQuarterlyReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentTransitionReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as a transition report.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Forms 10-K, 10-Q, 20-F<br> -Number 240<br> -Section 13<br> -Subsection a-1-<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentTransitionReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentType</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressAddressLine1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Address Line 1 such as Attn, Building Name, Street Name</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressAddressLine1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressCityOrTown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressCityOrTown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressPostalZipCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressPostalZipCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressStateOrProvince">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressStateOrProvince</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:stateOrProvinceItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCentralIndexKey">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:centralIndexKeyItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate number of shares or other units outstanding of each of registrant's classes of capital or common stock or other ownership interests, if and as stated on cover of related periodic report. Where multiple classes or units exist define each class/interest by adding class of stock items such as Common Class A [Member], Common Class B [Member] or Partnership Interest [Member] onto the Instrument [Domain] of the Entity Listings, Instrument.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCurrentReportingStatus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' whether registrants (1) have filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that registrants were required to file such reports), and (2) have been subject to such filing requirements for the past 90 days. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCurrentReportingStatus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityEmergingGrowthCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFileNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Commission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFileNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fileNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFilerCategory">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicate whether the registrant is one of the following: Large Accelerated Filer, Accelerated Filer, Non-accelerated Filer. Definitions of these categories are stated in Rule 12b-2 of the Exchange Act. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFilerCategory</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:filerCategoryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityIncorporationStateCountryCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Two-character EDGAR code representing the state or country of incorporation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarStateCountryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityInteractiveDataCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-T<br> -Number 232<br> -Section 405<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityInteractiveDataCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityRegistrantName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityRegistrantName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityShellCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant is a shell company as defined in Rule 12b-2 of the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityShellCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntitySmallBusiness">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Indicates that the company is a Smaller Reporting Company (SRC).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntitySmallBusiness</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityTaxIdentificationNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation 12B<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityTaxIdentificationNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:employerIdItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_LocalPhoneNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_Security12bTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_Security12bTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:securityTitleItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SecurityExchangeName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Name of the Exchange on which a security is registered.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection d1-1<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SecurityExchangeName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarExchangeCodeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_TradingSymbol">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Trading symbol of an instrument as listed on an exchange.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:tradingSymbolItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>63
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6634004336">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2019:</div>

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

<table cellpadding="0" cellspacing="0" id="zcf07523367524c41877d56d489917e98" 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;">One year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After one year but within two years</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After two years but within three years</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: 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; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of Investments</a></td>
<td class="text"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following is a summary of our investments (in thousands):</span>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" id="zb56166283a7847d5befc091adecaa6a1" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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; font-weight: bold;">September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">752,495</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,484</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(148</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">753,831</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,589</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(45</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,865</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331,371</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">264</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331,618</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,986</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,963</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,948</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 13.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,297,389</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,073</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(237</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,299,225</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">539,820</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,108</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,767</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106,536</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(137</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106,500</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">34,692</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">(38</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,654</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,283</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,302</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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;">690,331</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,234</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(342</div></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;">693,223</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,987,720</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,307</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(579</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,992,448</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">606</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,988,932</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5,307</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,185</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,993,054</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="zf8befa7024ac4c7aaab0e6b0e3be21d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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; font-weight: bold;">December 31, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cost </span>(1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">956,879</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,858</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">955,034</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">168,839</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(104</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">168,738</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">244,640</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(77</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">244,578</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63,572</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(323</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63,249</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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;">1,433,930</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,362</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,431,599</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">299,018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">194</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,286</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">297,926</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; 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;">107,789</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">194</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(109</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">107,874</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,600</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,576</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,980</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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;">(287</div></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;">16,693</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">439,387</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">388</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,706</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438,069</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,873,317</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,068</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,869,668</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current 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;">1,212</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,349</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 22.5pt; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,874,529</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">556</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,068</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,871,017</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze2689b040009421da56fad38f1ad9a5f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our available-for-sale securities are held at amortized cost.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z4c2e520a6c644d0f8f16eee8ae381f87" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 18pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z94b340357ef0469db6ab0f6c9e7f6ab9" 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;">We recognize our equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock', window );">Temporarily Impaired Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments we consider to be temporarily impaired at September 30, 2019. 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.</div>

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

<table cellpadding="0" cellspacing="0" id="z78a191fc6a1c47b5bbf4c2cc8e099df3" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" 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"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;(In thousands)</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">104</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">304,705</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(268</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,675</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(41</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">336,380</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(309</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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%; background-color: #FFFFFF; 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%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">102,733</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(156</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,974</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(26</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">125,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF; white-space: nowrap;" 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,918</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">(55</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#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;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,918</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">(55</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #FFFFFF; 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%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,498</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" 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%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,597</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,095</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; 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: #FFFFFF; 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: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(33</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">154</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">486,854</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(480</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,246</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(99</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">557,100</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(579</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
</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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=118939692&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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>64
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6817062176">
<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">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our consolidated balance sheet.</div>

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

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

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

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

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We added product sales from TEGSEDI to our commercial revenue in the fourth quarter of 2018 and we added product sales from WAYLIVRA to our commercial revenue in the third quarter of 2019. </span>In the U.S., we distribute TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that takes title to TEGSEDI. The 3PL is our sole customer in the U.S. The 3PL then distributes TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distribute TEGSEDI to health care providers and patients. In Europe, prior to the third quarter of 2019 we distributed TEGSEDI through a non-exclusive distribution model with a 3PL that takes title to TEGSEDI. The 3PL was our sole customer in Europe. The 3PL in Europe then distributed TEGSEDI to hospitals and pharmacies. In the third quarter of 2019, we entered into a distribution arrangement with a 3PL and began to sell both TEGSEDI and WAYLIVRA directly to hospitals and pharmacies in Europe.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We provide details about our collaboration agreements in Note 7, </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;"> in our Annual Report on Form 10-K for the year ended December 31, 2018</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">.</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under each collaboration note we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za828ef045c5342ec950720727f58194e" 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z423ff748c87641c8b173de2f4fc02db9" 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" id="zf1c5606cc4d545ceaeee39b9216b6706" 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" id="zd1b38b04c6d44ee2a317b490bdd9a611" 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" id="zdc1a47e8a7f84ce9b17a88c78aaa2813" 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 is probable. </div></td>
  </tr>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z154b7c49dc104a57ab977ae0e4e30809" 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;">2.</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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Often times 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. These items are contingent upon future events that may not occur. 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0c7f5c3635d344b3a58160ef8667cdcd" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 are usually based on scientific progress. For example, in the first quarter of 2019, we earned $35 million in milestone payments from Roche when Roche dosed the first patient in the Phase 3 study of IONIS-HTT<sub>Rx </sub>(RG6042). We did not consider these milestone payments probable until Roche achieved the milestone event because the dosing of a patient was a contingent event that was not within our control. We recognized the milestone payments in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payments.</div>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6b0a5e16e14f413e9cb3790671d564a2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
  </tr>
</table>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z1050d76f512c44499a8a4a55c6cd90ec" 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" id="zc0968e72382e45d9a26ab5eae98b5ed7" 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 on future product sales;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zdc34827c6d5d41dabfa0b3a3713d80db" 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;">Contractual milestone payments;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc92b502b421a42638f6c4797795c4af4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses we expect to incur;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc9eaca6cecc84fc5a8f56282da85c4c1" 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;">Income taxes; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z9f345c6a9ccf4de79419b350e5a3fc46" 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7a4859a1235b498a8927bb7e99a59f30" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of internal hours we estimate we will spend performing these services;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z479e033d5771475ab32e613cf9bf9239" 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" id="z781255f68a404a85aa0ec8ffb0f8d24f" 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" id="z6ce136f034fc4177890b3f2eae4d4f3a" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</div>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb5abc673cc6d48aa89e5180f190cfad5" 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -54pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. For example, </span>in the third quarter of 2019, we updated our estimate of the total effort we expect to expend to satisfy our performance obligation under our<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2013 Strategic Neurology collaboration with Biogen</span>. As of September 30, 2019, we have completed a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> significant portion of the research and development services. We expect to complete the remainder of our services in 2020. As a result of our change in estimate, in the third quarter of 2019, we recorded a cumulative catch up adjustment of $</span>16.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to decrease revenue. We expect to complete the remainder of our services in 2020. Refer to Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further discussion of the cumulative catch up adjustment we made.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>

<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Commercial Revenue: Product sales, net</span></span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize product sales in the period </span>when our customer obtains control of our products, which occurs at a point in time upon transfer of title to the customer. We classify payments to customers or other parties in the distribution channel for services that are distinct and priced at fair value as selling, general and administrative expenses in our condensed consolidated statements of operations. Otherwise, payments to customers or other parties in the distribution channel that do not meet those criteria are classified as a reduction of revenue, as discussed further below. We exclude from revenues taxes collected from customers relating to product sales and remitted to governmental authorities.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We record product sales at our net sales price, or transaction price. We include in our transaction price estimated reserves for discounts, returns, chargebacks, rebates, co-pay assistance and other allowances that we offer within contracts between us and our customers, wholesalers, health care providers and other indirect customers. We estimate our reserves using the amounts we have earned or what we can claim on the associated sales. We classify our reserves as a reduction of accounts receivable when we are not required to make a payment or as a current liability when we are required to make a payment. In certain cases, our estimates include a range of possible outcomes that are probability-weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflect our best estimates under the terms of our respective contracts. When calculating our reserves and related product sales, we only recognize amounts to the extent that we consider it probable that we would not have to reverse in a future period a significant amount of the cumulative sales we previously recognized. The actual amounts we receive may ultimately differ from our reserve estimates. If actual amounts in the future vary from our estimates, we will adjust these estimates, which would affect our net product sales in the respective period.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are the components of variable consideration related to product sales:</div>

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

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Chargebacks: </span>In the U.S., we estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to our U.S. customer. Our U.S. customer charges us for the difference between what it pays for the product and the selling price to the qualified healthcare providers. We also estimate the amount of chargebacks related to our estimated product remaining in the distribution channel at the end of the reporting period that we expect our customer to sell to healthcare providers in future periods. We record reserves for these chargebacks related to product sales to our U.S. customer during the reporting period.</div>

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

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Government rebates</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">: We are subject t</span>o discount obligations under government programs, including Medicaid and Medicare programs in the U.S. and we record reserves for government rebates based on statutory discount rates and estimated utilization. We estimate Medicaid and Medicare rebates based on a range of possible outcomes that are probability-weighted for the estimated payer mix. We record these reserves as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. On a quarterly basis, we update our estimates and record any adjustments in the period that we identify the adjustments.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Trade discounts: </span>We provide customary invoice discounts on product sales to our U.S. customer for prompt payment. We record this discount as a reduction of product sales in the period in which we recognize the related product revenue.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Distribution services</span>: We receive and pay for various distribution services from our U.S. and EU customers and wholesalers in the U.S. For services we receive that are either not distinct from the sale of the product or for which we cannot reasonably estimate the fair value, we classify the costs for such services as a reduction of product sales. To the extent that the services we receive are distinct from the sale of the product, we classify the costs for such services as selling, general and administration, or SG&amp;A, expenses.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Product returns: </span>Our U.S. customer has return rights and the wholesalers have limited return rights primarily related to the product&#8217;s expiration date. We estimate the amount of product sales that our customer may return. We record our return estimate as an accrued refund liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale. Based on our distribution model for product sales, contractual inventory limits with our customer and wholesalers and the price of the product, we believe we will have minimal returns. Our EU customers only take title to the product after they receive an order from a hospital or pharmacy and therefore they do not maintain excess inventory levels of our products. Accordingly, we have limited return risk in the EU and we do not estimate returns in the EU.</div>

<div style="text-align: justify; margin-left: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Other incentives: </span>In the U.S., we estimate reserves for other incentives including co-payment assistance we provide to patients with commercial insurance who have coverage and reside in states that allow co-payment assistance. We record a reserve for the amount we estimate we will pay for co-payment assistance. We base our reserve on the number of estimated claims and our estimate of the cost per claim related to product sales that we have recognized as revenue. We record our other incentive reserve estimates as an accrued liability on our condensed consolidated balance sheet with a corresponding offset reducing our product sales in the same period we recognize the related sale.</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Upfront payments</span></span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we enter into a collaboration agreement with an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. For example, under our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">collaboration agreement with Roche to</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the treatment of complement-mediated diseases</span>, 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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 there is considerable uncertainty in the research and development processes that trigger these payments under our collaboration agreements. 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the second quarter of 2019, we achieved a $7.5 million milestone payment from Biogen when we advanced a new target for an unidentified neurological disease under our 2018 strategic neurology 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2019, we recognized an $8 million milestone payment <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">when Biogen initiated a Phase 1/2 study of IONIS-LRRK2</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (BIIB094) for the treatment of people with Parkinson&#8217;s disease</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We concluded that the milestone payment was not related to our R&amp;D services performance obligation. Therefore, we recognized the milestone payment in full in the third quarter of 2019.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. </span>For example, in the third quarter of 2019, we earned a $25 million license fee when GSK licensed our HBV program from us.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense. </span>For example, in the second quarter of 2019, we earned a $20 million sublicense fee when Alnylam Pharmaceuticals sublicensed our technology to Regeneron Pharmaceuticals.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zd501d31562294c6aaa719422cd15d756" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za3dd236033f64fc69c60fe14eb86f927" 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 at a stand-alone selling price. </div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 at their 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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the prevention of thrombosis. As part of the agreement, Bayer paid us a $</span>100<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and to initiate development of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which Bayer licensed. As part of the 2017 amendment, Bayer paid us $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the 2017 amendment, we concluded we had a new agreement with </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligations. These performance obligations were to deliver the license of IONIS-FXI-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, to provide R&amp;D services and to deliver API. We allocated the $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million transaction price to these performance obligations. </span>Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 7, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for further discussion <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">of our accounting treatment for our Bayer collaboration.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z647b2221962b4885b6203f5375ade9eb" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z24d42ec8f51f41848c8f9d33210e47e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf3b846712a0f4085b6899ba8ff04e10d" 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 contract receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer</span>.</div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 September 30, 2019 and 2018, we recognized $30.3 million and $37.2 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the nine months ended&#160;September 30, 2019 and 2018, we recognized $103.5 million and $80.4 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Products Sold</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of products sold includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of products sold. Prior to obtaining regulatory approval of TEGSEDI in July 2018 and WAYLIVRA in May 2019, we expensed a significant portion of the costs we incurred to produce the supply for each medicine we are using in the commercial launch as research and development expense. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We previously expensed $</span>0.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>0.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of costs to produce our products related to the product sales revenue we recognized in the</span>&#160;three and nine months ended September 30, 2019, respectively.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to Akcea&#8217;s IPO in July 2017, we owned 100 percent of Akcea. From the closing of Akcea&#8217;s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent of Akcea. In the second, third and fourth quarters of 2018, we received additional shares of Akcea&#8217;s stock related to our license of TEGSEDI and AKCEA-TTR-L<sub>Rx</sub> to Akcea, increasing our ownership percentage to approximately 75 percent. In the first quarter of 2019, we received 2.8 million shares of Akcea common stock as payment for the sublicense fee Akcea owed us when Novartis licensed AKCEA-APO(a)-L<sub>Rx</sub>, increasing our ownership to approximately 76 percent at March 31, 2019. At September 30, 2019, our ownership in Akcea was approximately 75 percent. In the fourth quarter of 2019, we expect to receive an additional 6.9 million shares of Akcea common stock as payment for the sublicense fee Akcea owes us for Pfizer&#8217;s license of AKCEA-ANGPTL3-L<sub>Rx</sub>. We reflect changes in our ownership of Akcea in our financial statements as an adjustment to noncontrolling interest in the period the change occurs. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The shares third parties own represent an interest in Akcea&#8217;s equity that is not controlled by us. However, as we continue to maintain overall control of Akcea through our voting interest, we reflect the assets, liabilities and results of operations of Akcea in our condensed consolidated financial statements. We reflect the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line on the statement of operations and a separate line within stockholders&#8217; equity in our condensed consolidated balance sheet. In addition, we record a noncontrolling interest adjustment to account for the stock options Akcea grants, which if exercised, will dilute our ownership in Akcea. This adjustment is a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based compensation expense Akcea had recognized.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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. We use the specific identification method to determine the cost of securities sold.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 September 30, 2019, we held equity investments in two publicly held companies, ProQR Therapeutics N.V., or ProQR, and Antisense Therapeutics Limited, or ATL. We also held equity investments in four privately-held companies, Atlantic Pharmaceuticals Limited, Dynacure SAS, Seventh Sense Biosystems and Suzhou Ribo Life Science Co, Ltd.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or market 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. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained the first regulatory approval for TEGSEDI in July 2018 and in May 2019 for WAYLIVRA. At September 30, 2019, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&amp;D expenses.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We did </span>no<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">t record any material inventory write-offs for the </span>nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Total inventory was $</span>19.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>8.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million as of </span>September 30, 2019 and December 31, 2018<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Topic 842 Adoption</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2016, the Financial Accounting Standards Board, or FASB, issued amended accounting guidance related to lease accounting. This guidance supersedes the lease requirements we previously followed in Accounting Standards Codification, or ASC, Topic 840, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>, or Topic 840, and created a new lease accounting standard, Topic 842, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Leases</span>, or Topic 842. Under Topic 842, an entity will record on its balance sheet all leases with a term longer than one year. Further, an entity will record a liability with a value equal to the present value of payments it will make over the life of the lease (lease liability) and an asset representing the underlying leased asset (right-of-use asset). The new accounting guidance requires entities to determine if its leases are operating or financing leases. Entities will recognize expense for operating leases on a straight-line basis as an operating expense. If an entity determines a lease is a financing lease, it will record both interest and amortization expense and generally the expense will be higher in the earlier periods of the lease. We adopted Topic 842 on January 1, 2019 and adjusted our opening balance sheet on that date for our right-of-use operating lease assets and operating lease liabilities. At adoption, we recorded $13.5 million in right-of-use operating lease assets and $18.5 million in operating lease liabilities, of which we classified $2 million as a current liability. We adopted Topic 842 using the available practical expedients<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> permitted under the transition guidance within the new standard, which among other things, allowed us to carry forward the historical lease classification of those leases we had in place as of January 1, 2019. </span>The adoption did not have an impact on our condensed consolidated statement of operations.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determined the lease term at the inception of the 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.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our current leases do not provide an interest rate implicit in the lease, we used our or Akcea&#8217;s incremental borrowing rate, based on the information available on the date we adopted Topic 842 or as of the lease inception date in determining the present value of future payments. Our right-of-use operating lease asset also includes any lease payments we made and excludes any tenant improvement allowances we received. 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">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.</span></div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">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 United States Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. We evaluate patents and patent applications that we are not actively pursuing and write off any associated costs.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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 style="text-align: justify;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act of 2017, or the Tax Act. The Tax Act created a new requirement on global intangible low-taxed income, or GILTI, earned by foreign subsidiaries for tax years beginning on or after January 1, 2018. The GILTI provisions require foreign subsidiary earnings in excess of an allowable return on the foreign subsidiary&#8217;s assets to be included in our U.S. income tax return. Under U.S. GAAP, we are permitted to make an accounting policy election to either treat taxes due on future inclusions in U.S. taxable income related to GILTI as a current-period expense when incurred or to factor such amounts into our measurement of deferred taxes. We have made the election to account for GILTI as a component of current taxes incurred rather than as a component of deferred taxes.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate long-lived assets, which include property, plant and equipment, right-of-use operating lease assets and patent costs acquired from third parties, 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The preparation of condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States requires 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 those estimates.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Income (Loss) Per Share</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net income (loss) per share by dividing the total net income (loss) attributable to our common stockholders by our weighted-average number of common shares outstanding during the period.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The calculation of total net income (loss) attributable to our common stockholders for the three and nine months ended September 30, 2019 and 2018 considered our net income for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net income (loss) available to Ionis common stockholders for the calculation of net income (loss) per share is different than net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the three months ended September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z00eabc01c7314802ada313966d09d4ee" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,221</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.34</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,772</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,772</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,930</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,551</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net income per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2019, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="zc0322252578341de96a258c078f8652b" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,681</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.40</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,174</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,174</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,938</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z7d625624b94545638eb0f4e059ddf991" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,538</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.73</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47,843</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(47,843</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43,226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,617</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,346</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.03</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the nine months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>September 30, 2018, was calculated as follows (in thousands, except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z75eaa0c4d75e40bdb6bd799da97a5c34" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis&#8217; Portion of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea&#8217;s Net Loss</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common shares</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.93</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,680</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss attributable to our ownership</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(110,680</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net income</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67,517</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43,163</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.33</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

<div style="text-align: left;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></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;">Dilutive net income (loss per share)</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2019, we had net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the three months ended September 30, 2019</span></span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"><span style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"> as follows (in thousands except per share amounts):</span></span></div>

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

<table cellpadding="0" cellspacing="0" id="z7c675bede3cd4c01a3cee6b6bcbd2ff1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,551</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,993</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">844</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,158</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143,408</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.18</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our diluted net income per share for the nine months ended&#160;September 30, 2019 as follows (in thousands except per share amounts):</div>

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

<table cellpadding="0" cellspacing="0" id="z65323820a31d4d7eb7d2b21bf608876d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine months ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,800</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.81</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -8.9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,208</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: 0.1pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">793</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our Employee Stock Purchase Plan</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">142,821</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.79</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended&#160;September 30, 2019, the calculation excluded the 1 percent notes because the effect on diluted earnings per share was anti-dilutive.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three and nine months ended September 30, 2018, 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 style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z5651e0539b1741fda1231d28f3d75c17" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7e90304a08cb4b28bbe2c90004d5b48d" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options; </div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z503eee239a9647d2b0c553764a10ff4d" 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; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7ddd358f5ffd49cb80e76497ec47f5cc" 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for convertible debt instruments that may be settled in cash upon conversion (including partial cash settlement) by separating the liability and equity components of the instruments in a manner that reflects our nonconvertible debt borrowing rate. We determine the carrying amount of the liability component by measuring the fair value of similar debt instruments that do not have the conversion feature. If no similar debt instrument exists, we estimate fair value by using assumptions that market participants would use in pricing a debt instrument, including market interest rates, credit standing, yield curves and volatilities. To determine the fair value of the debt component we are required to use accounting estimates and assumptions. These estimates and assumptions are judgmental in nature and could have a significant impact on the determination of the debt component, and the associated non-cash interest expense.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We assigned a value to the debt component of our convertible notes equal to the estimated fair value of similar debt instruments without the conversion feature, which resulted in us recording our debt at a discount. We are amortizing our debt issuance costs and debt discount over the life of the convertible notes as additional non-cash interest expense utilizing the effective interest method.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> operating segments, our Ionis Core segment and Akcea Therapeutics, our majority-owned affiliate. Akcea is </span>a biopharmaceutical company focused on developing and commercializing medicines to treat patients with rare and serious diseases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We provide segment financial information and results for our Ionis Core segment and our Akcea Therapeutics segment based on the segregation of revenues and expenses that our chief decision maker reviews to assess operating performance and to make operating decisions. We allocate a portion of Ionis&#8217; development, R&amp;D support and general and administrative expenses to Akcea for work Ionis performs on behalf of Akcea.</span></div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, restricted stock units, or RSUs, and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. The expected term of stock options granted represents the period of time that we expect them to be outstanding. We estimate the expected term of options granted based on historical exercise patterns. For the nine months ended&#160;September 30, 2019 and 2018, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

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

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

<table cellpadding="0" cellspacing="0" id="z388354f7f2c8412e9e9de5b8e3459c1f" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63.1</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; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z30355fed305b46119b543b91f9afc38c" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z0872481741b0420bbd360700797058d5" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">45.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis RSU&#8217;s:</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. RSUs vest annually over a four-year period. The weighted-average grant date fair value of RSUs granted to employees for the nine months ended&#160;September 30, 2019 was $59.79 per share. The weighted-average grant date fair value of RSUs granted to our board of directors for the nine months ended&#160;September 30, 2019 was $64.65 per share.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our stock plans, Akcea has its own stock plan under which it grants stock options and RSUs and under which it derives its stock-based compensation expense. <span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">The following are the weighted-average Black-Scholes assumptions Akcea used under its plan for the nine months ended</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">&#160;</span></span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">September 30, 2019</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;"> and 2018</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; color: #000000;">: </span></div>

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

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

<table cellpadding="0" cellspacing="0" id="z360e42439bb8413992635f2432cb81db" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.7</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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">75.6</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;">77.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<table cellpadding="0" cellspacing="0" id="z8c29cc873e9f4c338c408f46e723b027" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">1.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">73.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">78.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.4 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; color: #000000;">Akcea ESPP:</span></div>

<table cellpadding="0" cellspacing="0" id="z71b9153bca524185ac553e8409da6e69" 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;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></span></div></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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" 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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">2.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">60.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; background-color: #FFFFFF;" 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; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands).</div>

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

<table cellpadding="0" cellspacing="0" id="zc27186a8ccbd43d89fd23ab27572bea1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"/>
    <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;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 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;">Nine Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">September 30,</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td rowspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><br/></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;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2019</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2018</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">Cost of products sold</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,744</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,780</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71,935</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,698</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">255</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,103</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,246</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total non-cash stock-based compensation expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,126</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,883</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111,564</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97,210</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the third quarter of 2019, three Akcea executive officers terminated their employment and entered into separation agreements with Akcea. As a result, in the third quarter of 2019, Akcea reversed $19.1 million of stock-based compensation expense it had previously recognized related to the executive officers&#8217; stock options and RSUs that were no longer going to vest.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of September 30, 2019, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options and RSUs was $143.9 million and $71.3 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 non-vested stock options and RSUs over a weighted average amortization period of 1.2 years and 1.6 years, respectively.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amendment to Equity Plan</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan to increase the total number of shares reserved for issuance under the plan from 16 million to 23 million shares.</div>

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

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

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors approved an initial share repurchase program of up to $125 million of our common stock. Our stock repurchase program has no expiration date. To date, we have not repurchased any shares of our common stock.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of Recently Issued Accounting Standards</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2016, the FASB issued guidance that changes the measurement of credit losses for most financial assets and certain other instruments. If we have credit losses, this updated guidance requires us to record allowances for these instruments under a new expected credit loss model. This model requires us to estimate the expected credit loss of an instrument over its lifetime, which represents the portion of the amortized cost basis we do not expect to collect. The new guidance requires us to remeasure our allowance in each reporting period we have credit losses. The new standard is effective for annual and interim periods beginning after December 15, 2019. Early adoption is permitted for periods beginning after December 15, 2018. When we adopt the new standard, we will make any adjustments to beginning balances through a cumulative-effect adjustment to accumulated deficit on that date. We plan to adopt this guidance on January 1, 2020. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB issued clarifying guidance on how to account for implementation costs related to cloud-servicing arrangements. The guidance states that if these fees qualify to be capitalized and amortized over the service period, they need to be expensed in the same line item as the service expense and recognized in the same balance sheet category. The update can be applied either retrospectively or prospectively to all implementation costs incurred after the date of adoption. The updated guidance is effective for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. We plan to adopt this guidance on January 1, 2020 on a prospective basis. We do not anticipate this guidance will have a significant impact on our condensed consolidated financial statements and disclosures.</div>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, the FASB updated its disclosure requirements related to Level 1, 2 and 3 fair value measurements. The update included deletion and modification of certain disclosure requirements and additional disclosure related to Level 3 measurements. The guidance is effective for fiscal years beginning after December 31, 2019 and early adoption is permitted. We adopted this updated guidance on January 1, 2019 and it did not have a significant impact on our disclosures.</div>

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

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

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8bdd29a294eb40de9936181c921e770a" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When a participant is considered a customer in a collaborative arrangement, all of the associated accounting under Topic 606 should be applied</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zcfd41a05fd534170aa5bf96451b5d895" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We will apply all of the associated accounting under Topic 606 when we determine a participant in a collaborative arrangement is a customer </div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z01a3ba1f007c4a6aa41b051b55d3c310" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adds &#8220;unit of account&#8221; concept to collaboration accounting guidance to align with Topic 606. The &#8220;unit of account&#8221; concept is used to determine if revenue is recognized or if a contra expense is recognized from consideration received under a collaboration</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf0bc1b58e5944c7c95ca172b59ca15bd" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We will use the &#8220;unit of account&#8221; concept when we receive consideration under a collaborative arrangement to determine when we recognize revenue or a contra expense</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8b99d6ac86964c488e342898b48a042f" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The clarifying guidance precludes us from recognizing revenue under Topic 606 when we determine a transaction with a collaborative partner is not a customer and is not directly related to the sales to third parties</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z991322bb7f8b47b487f7e37acfd889f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 72pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">When we conclude a collaboration partner is not a customer and is not directly related to the sales to third parties, we will not recognize revenue for the transaction </div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The updated guidance is effective for public entities for fiscal years beginning after December 15, 2019, and interim periods within those fiscal years. Early adoption is permitted. We plan to adopt this guidance on January 1, 2020. We are currently assessing the effects it could have on our condensed consolidated financial statements and disclosures.</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://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>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>65
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6992311264">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Leases (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Dec. 31, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 13,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">17,731<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,100<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_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201602Member', window );">Topic 842 [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_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,500<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Operating lease liabilities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18,500<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Current portion of operating lease liabilties</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,000<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in deposits and other assets 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">Current portion of $2.1 million was included in current portion of long-term obligations on our condensed consolidated balance sheet, with the difference included in long-term obligations.</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_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_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's right to use underlying asset under operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=77888419&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201602Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsForNewAccountingPronouncementsAxis=us-gaap_AccountingStandardsUpdate201602Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><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>66
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6633882960">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Share Repurchase Program (Details)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
</tr>
<tr><th class="th">
<div>Sep. 30, 2019 </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_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchaseProgramAuthorizedAmount1', window );">Authorized amount of share repurchase program | $</a></td>
<td class="nump">$ 125<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockRepurchasedDuringPeriodShares', window );">Shares repurchased (in shares) | shares</a></td>
<td class="nump">0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_StockRepurchaseProgramAuthorizedAmount1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of stock repurchase plan authorized.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchaseProgramAuthorizedAmount1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockRepurchasedDuringPeriodShares">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares that have been repurchased during the period and have not been retired and are not held in treasury. Some state laws may govern the circumstances under which an entity may acquire its own stock and prescribe the accounting treatment therefore. This element is used when state law does not recognize treasury stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=109259400&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI http://asc.fasb.org/extlink&amp;oid=27012166&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI http://asc.fasb.org/extlink&amp;oid=6877327&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchasedDuringPeriodShares</td>
</tr>
<tr>
<td style="padding-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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>67
<FILENAME>R42.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6633317392">
<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>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax expense (benefit)</a></td>
<td class="num">$ (14,915)<span></span>
</td>
<td class="nump">$ 452<span></span>
</td>
<td class="nump">$ 9,204<span></span>
</td>
<td class="nump">$ 824<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_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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=26873400&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=109238882&amp;loc=d3e38679-109324<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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>68
<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>ZIP
<SEQUENCE>69
<FILENAME>0000874015-19-000130-xbrl.zip
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
begin 644 0000874015-19-000130-xbrl.zip
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MJP$I^#H?]'N?[@<$+H?0>#2^(@?#=^1F-"9 9' W[%V3WLT%W(2[OXP^75_
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MN1$UV> D47H(3;?0\WG,Z:\]^-]"6JX/$3<J6SI=%,# )@O9Y'?@<1K.UC+
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MO]T7XD=+.#O"_VA '*C_+>'_ %!+ P04    " !&?69/V(Q\T Z0  #"!00
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MLW6-#.MLV:QJH2T>Y;PHEW@QGU<?X/:/<-%*W*R&!H?RJLRNU$X/WH]#7U3
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M7YU:I^<OWUR\.T6'M.F"EN?K>/I(';%GXJ*,L$%^+?$$KVZM<PINL+G:?%%
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MZVO0/&ETR'[6TI)'YT$[?<EKJ<1)>@[W<VH?2BF8FP9>A6'#2X1O7^GR$_$
MQ+0R3" .1%K=4FP5)E, Z0IZ(DB2^4KJ- 6Z3LA=1:R9"-X 93<!V24?P%OJ
M!1-!%'$!B"$IHIX8'X^_6+G'+V\N+M[\<7HA58YWUF^GYZ<7QZ_Z['UF_7%\
M<7%\_O[L5!2%G+SYWZ?G\/<FDU=MZ6;U%#524T4U?'J&MBK4+U5J8H2\9R1
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MB-H-T7_HXSU ^NL?O@4:9%$8Y%GLIWG@A]CSU(^R@B4V<WPO*/:7!O<>TO\
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M3V*RD)Q:V$MI2EN%N#IC/NF]-5@/R09;DPW"0[+!EB/V#9E3<>'$09'E"2O
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MHR&PQF R=@,CY=20:2WT4?X1.,F2SS20J<SD;M=#)GK?P1(9 74>M>>F9T_
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MC"B+$V!KO0+\9"KZ9>QMO42C[\UBEH3WC/&DZ^8JR06,0!F,+'8FB[(69[.
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M*<=Y AS]-.M,VCI;&[O(LV0$,DZ5 C(L$"PGFZK+/*=0N 5V"7ZXW0H)\I!
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M6;LV+T6NW5<GU_XU()T)D("C=71)5T_M?,]!WY*#[@3]'K\Z_7876%:=XS6
M=VV6S.F>@O<4O"T!3;IGO>.+ 1.K#XU#TWP]RAV#U#QF&O5>6-B>6#^UL% D
M5>_U2'4T/NT,^_\MW:K=L\YX^I3>RYI8[4[CD!A9XY"RC7_J3M;-LH!!P]%_
MQ5=+W@G_CE/3W[%(2H4*U$_YW_*O__U'L(CN\8^KU?6,_?'_ 5!+ P04
M" !&?69/3*"VD! )  #X,P  "@   &5X,S%?,2YH=&WMFUMSVS86Q]\[T^^
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MCW$.;VC P4Q96:DKLU@"-%Y0P&H@M\#>[,=+HQNO(-DL7/^-43Z"F< <A8@
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M""VQ?@-=LFP!&]M+C-6GMVQ]U<RV&D?;HH(Z8XMU>^]#9R#[6J&QR4S?D,_
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M0 -"E5/SSB106D@*F4F-!2QS[6XT1M##@O4 "J^ 2@P31/(L0QX! ,5I2A2
MA$!DN!*"60HQHU0*M6"U>'6[)'J$@QY%,3;0KLR-DU&I?S\O!\XZ'<Y.MK+_
M'.>CJS4?NQ+7#H,?DB#T3VB#$G&R!6[/BO:9EQ<73I,/O<CM)?_YU"J^O[@6
MST>R.JPF26+_(P=C>V2KDW-9S>>)<:&MU$A28SFAE$A,"+'..&8Z%2G*EM+\
M9%[SWRA^\(JDMV?V AI,-(&,&46052)U=@NQ;EXSZQV!I8S_%_4"O 5@J<0U
M67F$CNU/R=(=KWLY[(]'YV7EX&#F.JRA@3#-M$VU))1@A0&UT!@)J;!DR5(5
M<+[#8-73]DCK!646JTQRDD(BC%7(M;LN2,TPYH@L-5TO:CT&H <F_U]BTH9U
M%Q)YW8?><R?O<#P:CF3A8S^WLM$PEA1K(B$@J4%202[3C!B#'&"S!;.WJOX_
ML_G[P^'XULQ)*Y452A,F.,$@E1YV&!EBF%+*--AR2)R7@*EWM9>8.3?DJYDJ
M2!6TE$F6I92H3'&K_%N1 FVU$LNMF&YDJ@1GE@&KG)B0Q-",.WQ9RSSP0$H6
M90"OJN6^F(1 O,?1HHIU#Y LK]M?3UQY,Q.)'"4G]G)4)QDG&/02#ZGDAW$A
MQ\;9"N;'^A<?K9Y> >LK>"]Q][RT[A%?[> J1@FW+] Q1Y#::IC?(4"@3R;"
M"&89$3CC@LF,IIFCAL5"-7JF&%ED++0HSA&YL]W<@9EF*>=80NV4B',:A%$9
M,QP[C0*<>FRT1EHL@-JR JA]XY2TFR<Y< Y0;MP#$SVIQA=CA*'$?M988/D:
M#4<.#/O%M##CG+29$S09H2"S6D/ !-$P%5F:ICP#E@+F]'&32AKU$!0](&*M
MT\BI3G$*0H7\SAU+8$H(ME(;0MT+B%-E+6JRP"GJ <)Z*&TYI[8O]MS7>GPQ
MKD^82\K1N?.Q_3F>E3VWQ= YU\F@',8LG$T+GD9\A!^>/"YA!HQ#CXO=>5A,
M#E'X[+!Q8$>'V:G\/E^3,9.04JN$,H305 I%TU0I8WS:#J7@M:I]6(_USN/R
M*.UA%MY>PL?]B57.[H^1M)&TSR"ME-*O"<I,"$0X$()Q0*6AUF"A^>L=_V5(
MBU$+-^,U2=K6[TA:O8UB;);K/&Y'BIL;5B@VC^U(YH4U>[(JW-0/YP#W<8*W
M^>4%SC)#$()6:Z*%4=KO<( I%QIF )EUF#<\9;V4;C@A>36;'MIB]$2Q$,7"
M8V*! 4%%)A6W&A#+4HX-%88!2BDAJ5D0T%R] 24HZR$1Q<+:S:IV;*S:+XM\
M.$DS7)C9'5W&+KJ,C\NX^3S_O1H%\XLTS&34")SJ3!/!4TXT01H"#!$4""S(
M'EWEIBM,-R_,8CY%Y-#K.,0$-088H 5C?LU3IIE/"*4V34EJ29-'RL(>(+P'
MVEZ,NO51D)5LR)H,ROS?O@20+^%<#@8^E3*?5HYU+Y+^[]K*Y/3<N@&U8S<>
M[L[[A7X;_:/H'ZU,['W)B[)RPFY6LGA^"<CRE#B/2!BM"6-&I(SX^OL(95PC
MK1NMZ 9[E'7"!XH57");U\'6U!>)(YQEG!HB,LFSE!D.,HTHQ,0\5%)]-4F?
MH@?XAI.F6U*]9=EF!AAYV$C,X=GC%;Z,VY2;]:JV;M(1<T;O8.Q1<#2I0=P?
MC:I<C4=2#>QI>=N"7B 9H="*&((SJ1"A%$G#C65I)G &,L*7VP_WXL(9@O4$
M;4DMNHU%12++(\M?R7(J4FA-2CS%"1+8[QW+B" :\,QDH-GR.)"SGIOE#K*\
M>0N(-!NW24DC1>WJ+:U!6$1/CE\(LM*48W\,T+/F^K5S]I^KGH072=Y-]'SI
M\F+]PCP:]W:>HW7_=TZE=G]+J0#$"!.A"./^=/9&-_AP07J";SCN_4RV;=YT
MBN(@BH.FQ $1J3>O4DE32VQJ%-""&ZH4$P0ALUPAHI>* TI9STF=#HJ#J8WE
M_O&VKG]5]TA5R;MI[Q[\:%%G_.%[MEI!]4!K$ZG]3B)97/G%J?KTOK=+MD@/
MK*SJ,3R_MLA&Y>7T[K-/9N,X?>3TKLWW[6>/C@_XYW?UO]?M7]"/2WEF=U1E
MY>\[,G//?B\'W^35T-_CO)I=-.E-#8<$>$C,( / C2B8?@9^2LZM%Q=3"WT&
MF8F 6(BFV5?S8_KF'C@6=&*MB)E\\&W:-^5DB!ND_<.#_9/DZ$_]XR_]W;W?
M3O=W^Y]/>LG^P>[;#;9J]_#@X][!R=['Q+TZ.?R\_[%_ZMZ<G+I_ONP=G)XD
MAY^2PZ.]X_ZIZ\#)!EOZ0UXDH_-R/'3^AONI_:[MY<@+2G_,YJ0N3R(O'%I&
MPQ\WV<S?KHO]/(:_6L"Y=@P&4T%:ERGR[[V(G+WW^N9?PF"$.%>"*$T<^KDR
MB*409-C0U*3BS6JT8W)?#=QEW3R7W[S>%U[DIJ_>0GS)4^BSG_)DM.EA[[U!
M,)Z>5TYU?7'?G ^3O<)8,[41UM^46W6QFK=4%H: UN.2;#/@#O(BXNUY>%M-
M7#%<68HZ FT?T@D91W%R7S>Y/$YN=R<W,K?#DQLT<U>BWH-(V3ZV7VTQMJL^
M,&/E0%U+8'\=O(XC$T<FCDQ0@G1U)V382N=RD%11J$:"Q)&)(]-BH3I;%TC1
M"HL\(W9/^))T)4?!'>T?'/?_KY]4Y94<K/]8UO JT;8YMR2(Q)&I9^0/DM[U
MJ;GNHK_FH_/=\=!UP59[WZ?YO/WAT+K_S)T"DXI9@:3E! AB,)/6$$Q$!D5F
M&24+:T<S $?E+,GL[T=5:<9Z=%B=V.IKKFW_>S[\^PSGQS.8?ZG#X:M(0>%^
M3^*&SZ@.*?,LLCRR_"F6<Y295 A ,T6(RHB"+%6^; *5B$FY8 \QOV8YWPC+
M&>@!V/(*V)'ED>7K9'FF0:J%1E I0QS?N<5"I)0I S).R,)JBG"CNAQ!V..;
M3B:--(\T;Q/-A<5064TP@HAD3/.,8TDRG%*+*5Q88N":YIM1YM#GC)/PRH]M
MK@C!0]&*%]4;:"Q:,<5),G1S[*XK;).UHL/99QS.+N(@]@B_3EI12AE'""-I
M-#&"*6@LD]JPS!*9(?K" ,/TPQ7**-@3I&VG7,0*B9&.SZ2C2;&2S-D.1!,!
MD0(9H#B#A&--D5ZPE72I2,#KZ?@OZVXAA^=^4KFS;'Z*5(Q4[#05-17(I@ B
MC2A!..,F-<I@Z6A&1+KXV,8EW/65:T;$-W\^0J1CI&/#=,29,BGG$D!M".=8
M**(R38"$F%"VB(Y+N=51,\95_\\.#,70[]WVY6HF1T-.$@"N9CE8VYX&L'%Y
MU;HP8*HL9IP;(;*49":3UJ:,2::-3!D "XJA+^587V.U7TS.O6LB[-\#/*[@
M1X)VFZ# 5VQRUKW!*2=^G3VE4$CDC ECG'6QX.S6I5SM=1 4HAXCX9T>&1D:
M&;I*AB(M$4BEHM0*DCFCWZC,&LY38Y#5BV/32WC@:V$H[%',(T,C0SO-4&@!
M5!@#YXL#PI 6R ?,H",I8 R+EZYUKX6AI(=PRZW<<->\[^^.6HVK/JDPJ^_M
MD8H+WS&>^$SC@D$E(4<II1E1VAD,AB.,)8-"I 8O+-JZA']^LWUO=:)*I#TJ
M6GZR661D9.13Q@24G$,-K<"68&"EIEDJM,J$)@S31<<'+N.0-\%([ASP-#P'
M/#(R,G*E:VY8 $RP%3)+B:%48J8T4@Q:9:21"W7D$@YX$XQ$J8]:QP2Q2,EN
M4]+*E'!K:.HX2; B7"G$D>&8 I')1<M*2WG<35 2<M@3K.647+V+O>83>5=3
ME>38#JVL]'F]0FX<@@?EY85[Y,S_=G QMO*S.)"JK.0H_VH3>599ZZ]J<A=]
M/-YS9>*Q)<=[OG*O;68PQE91+A!QWK]S^&$*L-69I>ZS!2'+I?S^&4'ZA?EX
M0X]I4W_SY-B=YT;_FAHKW).+>E#$TX"CN(CB8H5!"6$L-%(+QB11,A6,*,LU
MDNXC0A;;6TL$)0(0%Q3U* [LW*@H+J*X:+6X<"X8H01) PPBQLD'09S_124T
MR!+$%E3R6"IB$H"XP(SV.([F190745ZL3EZH-'.2 FB)A""48<[=.V-2090S
M,LB"%*>EPCD!R N$TEZZZ=HAC<B+S86$5I2*,=E(L9I4C.;S+^*IYQL5J:V+
MD&>:264T-YFQA$&MD,ADQA4V "MH%QQQ?B? LZJ2*EQL.+VLD:/.([4CM3=%
M;0.Y)JD%%%)-% 5<Z912A*!F)H48/QF,64WB:-K#8L/+6I':D=J=HK:5V/CM
MDMP23;0D(@,VI<X#DA2GV#R]UV,U(5'>$W##VS8BM2.U.T5M02@4Q!A$4T.T
ME0(JG$)@W7]6HT4&^9T8QRJH30#KI6E+ECLVG*&RSB!@W"/VTCUB@0Q)$)F-
MH0U*Q$G$2<1)Q$G$2=PAN_2RS$H.8MW[?FD+9X6O^M# N+7@Q5L+ AF2( 1K
M:(,2<1)Q$G$2<1)QTKE]5J%OJ=HMAZ.DS)++20+7T(=]3:PS&HJ;L[[HN@?"
M8?;'LC3#?F&F:7S#$X>&^6KDQ$IA$!=& 0(84=(@98%B'*1I:K.U9+4(RH+;
MS1G#!I%/+^ 3SC#C6AA N"$&2&6IK\N;&8$1-AEK)I4D_%KAD4Z13B]13X@1
MI# T("4DE9"+%#%J,IIE2%/,UY*^@7N8A7<01F149-0+&&64Y4XU<:HS2#!+
MI<@@YH9J##@FIJ&LB8XIJ#:%_U=;J*-WJTJ'K]IQ*4?N95P6""4\T[R\<:^&
M[V> F-L'YH3.40V&Z6+1G-210NI,.TG"+",$:^G<36$SQ; Q!,BGJV.L),,:
MD!ZFL;Q>9%:'F)5:S2ACCBW&$N@H)2GE*4LQ %II_'0AB155DD5IRRMR16)%
M8LT3BVJ_/X +YV\2DNE4 &XT!4R"# "2+3QH:?6N)Z0]0<([\"$R*S+KY<:@
M-$9((H6BEJ0&"VJY%9H;P5*-Y8*@3@.)^QC 'DS#"^ML>'6SE54D3^Q@X!K=
M2\YL82LYJ/U2:2[R(A^.)J4H B@D$&NS=*4VRQ1O?YR@S4FZ_BVLW9=XG*=
M( (4SPB1 $J$(!580PV04F@][B\%/8 W[/W&0DN1S&TG,Z169XH0AA GW&(N
M!+)*:"D !A(O2)EHP..FO,=@2^J 1#)',H=*9I 2;:!4(L6,6&4XI\(P1CD3
M4C"RX+36!KQ\!' /TY;4!XALCFP.E<THRX@4 FHK"1%4<4ZTLH"G5$""^7HB
M"Y#Q7DJ[6-$T5BB<JU!87EH/P^(LL=.]<0'$&#84"XVU41I)YO%I/+.-E_-2
MCK!4&RQU9A"Q5"OEDW<LT<*F BJQIDJ$J;-9NECX)/(V\K81WDJ#()"<2@PE
M<<P5@J:*4, USBQ97+!H]64&*>YM?+]%Y&WD;8MX*ZDF1G!%L?#^!-?: .L4
M+]=6&;A0WZX\1I BW*,\ZMO(V\C;)7E+,I6!3+O_$TB0@HK(S!J%L)(V9=*L
MIT @$ST&6[+LMN'D@U@@,)@(8?A#$D3N66B#$G$2<1)Q$G$2<1)W"*YY562_
MT.6%37X8E,/ACTE6E1>S)9*R:')I)!SO+AS?+0C/['"V0#9!QF>'B_D3ZJQ%
MG)"44R4)YII; 7%&H:+,4)&N)R42]5+4\A3P2*5.4.F'UW ):(00UHY %I!,
M,ID2B@@"2/(,<;["C,1A/;([CZ\P\%[*-IR:^&Q6K7(N?XS:KHL4?0U#&976
M9)I0+BG1BDF;X0QP0E.8*;%XR7[E2P@0I#V$-KR$$/5=)--K]9V!AE!#J70D
M(<*FREF.B#K"( J9SE88V%]&WS'4@VEX!0PWI^_BPD ,T 0?H(DXB3B).(DX
MB3B).(D+ PV>''0X.K=5DD]7!Z9[)7Z,YPAMFCZA#4D08C:T08DXB3B).(DX
MB3CI7*6MT(MJ[1=?[7!4EWF>&&_Q#*%0')[UK6K=@& 2B#^PH_D2F52G7$J@
M-81$*":PE0IFG+HOK!1P/1M1<0]NNJQ5#!Y$+KV22QFDC%L.E5"*2&$$PSH#
M-C5 2HS8>C:'BI[8=.&*2*5(I5=2"1A*$"491HH03A47)(784B*S#""#UU.Y
M6?0 #*\D>N12Y-)SN*25@3A33@-Q15#F* 0(I2S-* $LY0T=%W0_HY!!V&XN
MM2GNORH'<F0K!ZU9?:08\0\E\K+&1*X9"!8<7$*DU!!H!8#3U<H*9$&F))>9
MH1R0-1T)A'KNI\%)EIBK'%FY&58RR*7-THS85!-FC1!84:,I@@!8(NAZ:A3!
M'N*1E9&5D973BG^68T0M-%F6$06MI(##+,4I9X*";#W;!W#:(X!$5D961E;6
MK!1" 68 I1FS1$O!=:JR#*4R8P KN*!V>!/G&.$>QE%7-KG[H)5G(BU,NQLV
M*<)B??:52;Y@ZK,_M4W+@^R@+,K;V[46'+, ,Y,!AE)D4Y)A*+02P"@F)$8F
M-0N/67B9L[_4#F4"VE&/[?$(8UMLFR@8HF!X2#! R-),<L S20EE[F_Q_[/W
MY<]M'4F:_\H+]<1$.P)VUY%U=<\Z@I;D;NU:QYKT3.Q/&UE562+&-* %0%OR
M7[_U %*BI"?QP/$>@/0A'*2 =^3WY9V9P!1(MI3H6Z#O<G2!.HB-2LP+S M[
MSPN0=0FD78X"-+6K8H,P,@J5HE.^H\7[H1&/N_!"[QX6$P,3 Q/#LDX.O8-<
ME,>LH?@<K8S9FXCHHHK=LXZV-_M!0L\E/L,GAMT6/G![QU!"M .Y)(.H=!O:
M16$Y83EA.6$Y83GAML([YZ4V,@WBXRG1D:IM3==9J@6^_3 @HOYL0F6\X*[#
M8RQ)OQ[Z]^-L^MOC^K?'D\OJY;Q\/T_\AZ7@K'[O#-_2_/EX,IV-%^^NL_4G
MD_SQISS]?Y?UQ\]I<3[-'TK>/UH71-(8*6T(HGJ6D$.4%"F(1#'J4CK;1C9>
MD*I'1@YOEB!WC1P?1&\MB^D#HTC66"^E-,X#1!-1M\5P.9ADDY ='<=;G70=
M1D'N6[_DO@2!&?JLG6\6V]GH;"@:)86V]2P*GP*&)#"$Z##N:(*V'QGA]PSQ
MK)\/$:2#U,^B9*!BHRPI@'> -BL)-EBKI/')[38[X^TH#'"_"^=B.";&,3&.
MG;*<L)RPG+"<L)P,0D[VOG%HDPF:7>=BN.3O\$K^[N*@5L?SJL;OAY6,W7 F
M?2*?<M8"4X$8D]>!G-$V252&H&/VT':;AD:A[X%>FZGVVZ)^9!@?'HSO%&CZ
M&HYUD$GI&+T3&K2P0>AD2*M0%#@G.X-"&Y\I H9+^+F$GXF@3R)H\S>!(D4!
M&;R(:**QP><8-?K.&;=;R.&$D>I[B@E3 5/!D5,!)-(E9B6B([!@ BKG#%#"
M;+S5'=/_MC [Q2LF LX8#29,Q9$[CO"RG+"<L)RPG+"<[(&<'%WWS@M:O!\I
MM^S@X?K?0RPM_+IS]VHVK;Y<6Q-X,[1#7@?,0L:$X'2.RBEG;$(%122;=C/-
MW8^@[TDM0\K&,(2&6IW;B2% G8K5%)-/$*2+J"J*1)9&)PVTP=GK=YJ%)D;:
M[ML"HWV)B3(R]TFYH3 H,E)"YZ%(X4U2P5-&EX2(H2.!N8V\11CIOA,7K-P8
M0@]4;J)$*LZ'(K4&#,+;XJVWSL>H?>CJW]IJ9X@;.=BW/FN.\W.\Y:CC+2PG
M+"<L)RPG+"<L)_L=Y]]P9\@FXOIM/+_!Q6(VCI<+C!?4+*;UBDQ:LWPVO;BH
MA]N,KU>ZCB?-R:^)L#D[IWK)Z+*><?V"9Y/T'5>2<279QL(Q53 _C" XN2&<
M9],7'XGF]<R"FQ-#O!<Q12ND+N!=PJ*\ JEMCE$A=HZ0WU[[2'4X^TY-</<(
MX_N \"VT<E858TI6H-%&ZTL$ ]HH0)G]CF>!F9$7E@'. &> ;PC@V;@@?$HY
M5[WM4'L5O$/EA<B8$G4.Y-S>#A@I1J 8X QP!OBF !X+(!5K99"Y KQXTR99
MI?5>$VC?6?"PO9P0R!'(0S31.;?#,;;!Q]A83EA.6$Y83EA.6$X.*[<#_>=V
M/NK9^"S)\VPZ&<^;5^=83>.T3.54"WJ5S*FW[;??JLT_7TS3K^?3B^J2S'>8
MX+GUT@W!?<S3R_9"WNLVKWM3_VW3-^%!SF@?9WX/;_2&ITE:.)U,T9X$E&*"
M1=!:YJ"E<-A56K^%]A1E1]+V/([ZG@CK/X+$%, 4<+_RXR]Q0-32*UD2&)]!
MRQ "4O+6&^.U21EVFR^"D3'A$+A@7UINF%B86+9B6VBM72Y&>4$2=(98;%1$
M(B;5]K_*'6VF"2.GQ2$0"AL7_2/A>#G@H<:%USFF[%4&#S;EF&,4$# GHTND
MSF*4+::R[$CK@<TJ'IYUP7DQCD\./C[)<L)RPG+"<L)RPG+">;$;UV G \]^
MP/DX-9//4FAO:-;,SW%&'+#JWV4[7F?UZ[[J4YQ-J@#-7]'LM)75I3#?\%E-
M29" 9'#!@P@8E(H&9%+D@(SI#%Q])2D&-WU6]=YE%5_U5,5W\B"BX!RTZA\-
MQ\L#MP2M;B,"C2*I8@ BUC^"BA&A6*&BJJ OIF-XXU<S8Y\1P77$ZHZ,( XB
M1\YY,::7 Z&7]=C%N\HE+F<IG8+D%3H3BW64;$S"J<[:FZ_DQQYH9GAY"*3"
M9D;_:#A>'EC3S*"83/1)9ND<I"!0$64K)(+-1@1USQS9NF:&9C-CYPFRNY[S
M^YC9 &) 2UF>-Y=SRNW<FS3][<WEHIV&$_<@.-13\/%!G-57R':]@]V=H?5?
MU!X[Y9-ZGOB:7ES^%FGVLJSD\^7E8K[ 22L4G_(N2.V,2!A"SE!I%V.2U:LC
M 9!<S!V\^]4XCWQ8@1*(D3%[8H3UEE%A6#.L[PIK'Y"\RSJ1-)!4B%Y@=,$%
M8=KFAHYMJE^-VCP0UMJ-- QL+ ;#FF&]M[!.Q:!6WF*A"!%%D$ZK$JP)1;1[
M".X9+GDHK,/(BSTI)V98,ZP'#VMO<U10@(R*X)*NNKLJ:P0BLLE@QPZ1KP8_
M'@KK:H2+GO<>; 767*[2BNZ3\<5EE<V!QR0X@GRT$>3[!9"OQ/GF2$#RN22E
M$NKJ=2@5" V2LQY50;*=QM$62E;\?C HYY*8"8;*!/?,)7U.!6BU#\5HGU$!
MJ!1+EA:CM8ETK'85%ZT,+)O$!,,$LT>FA@%!!=KE 2BJEV81O(G16:-MML5U
M9DTV7[;BN#J6F8"9H%]3@X(#0\5D"QERBEX5@85"]3BL"((+5X9F:G#ARE<+
M5_)>A(DX:G[P4?,KJOTL>'XSX@,A:R%)IQ3 >-L.[0*@1#9%S+IS]_86BE?T
M",2>1'TX'<; W@-@QVI#44[!80%P$K 8K2UJ)XTT*=UW?1.7KS"P&=A# '8!
MGVUU?\ 5!"19(8W)H<Z!M$OZOO/P'JJQU<@K+C=E8#.P-P5L\I15#DJ4+$"'
M&-!D[[0B2J*84KB$91,E+/6A'<S?/EN>49PU?[LZNR^^U74RB=J%6^M'$59'
M>4K48&I#"#AYU\80)M,%S;^[XW&E"\+9\DJ>OP]T+*9OKK[C^IWKJWGUQ5>?
MNOTS_(]61KZ'__C;\O']\7><QYL*F&_CC/#7;['4[_X[7OR![^;M9YS/KG]I
M=39+H6A$*QC7@B/$!YZX>D_\HSE?XO%JU=>UX*S8HU.FKG]T\YH^^DQ$.DYB
MIW*S>N./JW.+TXM<+]*SER^>G3:O_G7R\_.3QT]_.7OV^.2GTU'S[,7C[WH\
MJL<O7SQY^N+TZ9.F/CM]^=.S)R=G]<7I67UX_O3%V6GS\L?ZH^>O?G[ZK_I[
MS_[S:7O$+Y\_;?[ZT\O3TV]Z//2_CB?-XGQZ.:]</>_U0'Z9X&6N))>_^9K(
MK5:.)+JXN&+09;"[?=URX_7K5N'\F;,M1=DLHT#(Q040-F>D@-XH"/+19K1E
M\SG_?PJTF_!]M'Y4N6O%W^:-E8=\B[WWM]RZI/++<? M"N/9^:QJJ^?U)^?S
MYNDD4[XR#G9_**?T9D&M@=54LV7[)DKG^LC=>!7'+' OQA.6M_O)VV8R=,/E
M4G4@HMW&9(8L1WQSU[NYGF_NX=Y<1NX!W]Q!(W<CZGWC(K-QZ=A)0'P78.(K
MPU>&K\SVR@<'WC?ZV8[@+9;_#:<V^T +KP?17_%J-BWCQ2=+LH*Q&%.Q(*(%
M H$@)02=;5#">-E1\K.%+;S2CT"K?O.'0VJ@8#P>!AYOZ7+H!"0X AF#28@1
MJ!W\K7P()F: J!'S;E?B*C'2MN>M=8-J8V"8,\PWH':]%@)ML386 M Y:I^=
M2VAM,=*(CD%Q6UA0&\)("]@S<+/:93QN0>VJ:O*2%K8",$)TWI/-&8H-Q2O5
M62&[S66QWHT<]%Q0-RBUNQ/W?TB-@K],9E2_]4_*S6L<3^:K( #-OVFJ/&>*
MB_I7T^5LO!BW']-V#4Y+L\"WNS57>BI"'DZ%\8[*AV]AM)>+<YH]GO[V9D;G
M-)F/?Z?50NP/0O2OZ46;-OAG%:66^%Y.3M]+S\EL/*\_>E)?3EZ_JD<PS2]H
M\;*<X=N;HQ>,!N>T%5HX$,8&LEZ@(>VL=M'JS<4)[L*/<B1ESY,P[UU:O,=>
M"<-\"%T".T!Y=A"-=:2CD""-10$A62!948]6X^:"#U]M)^AYF,*0VH$8C<>+
M1A0D$DDLF@",3A6:R2J31/)%>7'?L=,/0Z,=59^(\<AX[!V/_1O!U=Z5Q14T
M1B$H@R&Y6&(U@;%X:6+'VKRM!@GT\&)W_9G VY\OI/9@VO3CR]F,)NE=LYCA
M9'Z!2YQ@_N_+^>*W^L4['"%TZ]4:0M_RAY+!K1SJ1MN6[WBL V#<'Z<SJN=V
M+8MGK2BN/N!DDL\^".8U$=^-?"E$HR4F($=@;:F$&H$\BAR,MK)CN.Q6(Q #
M&_AVBUSL>4R"R87)9:OD$J55E(2'8A/8E)"*M=[DD*0W$#<8^+@+N>B!#4EA
M<F%R87)Y,+F@$BA2,DHJ"<;': QZ67(6@IR)G?,2'Q;'N5-)5\_E7$PN3"[[
M32Y#XI:,*-&5H(L)8*0.D:P$B4"RFC#ROG.P'Q@C/@A[I8^.DZV%;#ED_="0
M]4 N":<V6$Y83EA.6$Y83H8G)T?7CON10<^-N3VZ@8-P\CK\NVOGK+ZZN&S=
MD5?3V=*[6RQFXWBYG+-X-GTQG;0.V6QZ<5%_Y5D[C83FBYNCND7,T4OK(AH
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M?Q>"V4$GD/=ZY%3/4SN93IA.!DTG.V83%8I13AI%.H#V*L924%/PEHJ KA'
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M0?12)%L=/E.HHQKEGNC;>%::D<A('#82;TGW?@F*$%46)N92O 8J!4&%HKQ
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MT?DD/!!0((^&BD*=M0"=H*M[I47_9E2X]&Y4)7._0;S;5I7>JQT>??^"VK7
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M"I0"[<"#%%F&*)449.,>-";[43WF/0,L:V=&_P"T,Q43A8;L2["0I/$A!2G
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MPM<8U_&#B>?Y9\8]26MP3UI)D3,A>&FE17X_"K5D;/KL"*3;,SC>#5V\!;)
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M0^@E:)]CY<>1M+[M<-L5"8MB2GPW2I*41(&?,L]-TU!TEDSLJ]D0IG1[(XL
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ME:"4:E:4^K_FM^K#URJ(-C%\J#]^$*N?  E6'Z'2JS]>FB>B  -)A02\R]!
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MS#XK=*NJDX?^CKGKRA656R*NKA00R'Q6NE%P=5VRVYNBF[S8V:9K=C_MSM/
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M$ZS%?D9F3[W.R\6'](9N#='&ON-PSQ.A'U+B!F$4.'X:>8G/T]@F2-^##:G
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M!O$T[>%]8SAM&B5D6I9#QW%7DAR'5D]'^;RE]P^/NW.%>_X+Z<[_=VX_EH6
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M8^VA0<08*!2PR.R=5)DAX47:3'UR..6"E'R@/'/JN4"4,HJ"P43"R1(*88"
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MY]3QDZ6. P&T \PAP2E1)/R:RD^LQL[X!6G1]=MF.8,\PTB&D9/!B+4"64R
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M9X($*TRY<& ,ZZ@E10B@'7*W3M,"4#!BJ<62 1_[C,API%588RT5-U:I([<
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M+6?CA VG [=XN935EAB/PH?#\6P2IOM!34L14Q_#<^*WB@"6L[OR ;>#-\5
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MBK]]>1XMT!CQ;(WK;*T<VT4DNT@RW@BSOE@;>\=7>-4.9+O,:J?%V!J5W4&
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M-Q]^.@W$=DK%[47K[6MEVD4OGVFWNSAVRI/>[(G>E[30[A/1*2%WL^5S[\R
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M)ETK@D>+K^Z3-+)FY!/O_:.H=0@+!'BPS(CGT[^L!D "9(,@P0;0($O''I)
M+[5D_G*I7-I!EE,)?"HP]?)@JG7?%F74,!85 4(@>>I"C-& T$)9&M5Q?5O[
MM*%,C[$CE_#9BZ+S^NKZ;.RX55)V2\KN$]Q)2EL@QHI<%!Z$"4Y2<%29I&RD
MC)/]0.'/63>\L,,%)!ZQ4+S@IJ<9Z5Q8::GJ49A\S]%'UGDP0".C'@A$G&5
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MVB2H VT5 RF"-02XE$8()8B2QS91]U:E61^Y3E>!E@(M+[TYF5%<2,FMU,0
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MX3$JZU/*/?(X<5P9H95A0O-(6#B:?^3W]_]Y0\KG"TK>6S<()7N2LLZ!83E
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M'A0\V.E062OB'6C+/-!(+=.2")(C34!KO@]7Z@$]*$5'*)AP(ICPS?VJIAV
M!T5T!"NE)\&!L%0+:0P/EK&D@8F&)H:GY%PIZD)7^EUO:LN]YG3<'HOR7([Y
M<?@I3J9U/DY_6/TZ'OW7;]6'"R3;JSC#.>'#SO[[K/I"W#A,#M;S>NL"=:'Y
MVFVYZBZYLI\UUL/A<:X*-5WQ\_[PZ9?^:CT%K210S2*E%IP31F@;F+4V>>Z)
M;VB4UL'*LCT.IEM]SK80P/&[+A;&?^6,3[6VDB43I2:@G'=$<X+*%_64,4OV
M402N$S5F.Z9#%> HP'%:P)%0+7#:Z:A4 FFY-<H0R:T**0:O]E%LH92:+<!1
M@./4@2,XZYB3+O)<=E8H;21CA#AK0(EHR0DX?8JU<DQOSJ;FT;L69]%G]P-J
M&#L3HHV@F@^CJ1T<T).S=7&Z *];FLF_B++@W9GY%D?]9!*W50J/B3G*O!51
M.-""6P!KI/ )+420=.^%<UO)3>@1JGK,Z&YA[A9*.+Z^5@"E $KK@.(X.$F\
M="(Z""FX%"0AU,2@A#;N,8%_)^EUNH-)0&0/5>""2 61"B(=%Y&2,LJ")XZ0
M"#;)G//%F37::L9%Y"_5G77/*I7$] 0]<@YGP:2"2063@HJ41")Y< !&"..(
M,-)+[QG5P9U"/>,7ZBEK!8\6GC+\D>/DZM]PCGE+^\.974SRWB=W/JBIY0/.
MZ8_D%&6)!ANX LNTI13_409M=2#*D(52C3?&<#Y]Y$V4O'GPE88S!R9'^X,6
MR3JN:*+&<"<416IM?N7#-\DW>2E6&#'T)U<#>YUW/V:^<N/JR\7VKU_X"%\?
MU?=<??5'^-A,.&N\O^!F]F0WX.T8\S-OA[K7[:5DI_VES]E?N<O^JF/L[_/]
MN!<1/QT,1I\1!_"WT70XRNF-XYCB&"$Q5H/^,.=(#JO1;)R7!4<TB1F2AO4)
MC9WF7$H[L/G:R46,TZ\.1!AT)\)@SR$,M0MAZ%?-^(^<UG*-GK$Y>I?-,0^3
MPU9BVH4$>3W96CJVHY3=B'1"_G5=DYQK DLQ/M<:O\9!#^P$597OWO_ZPT_]
MR?1#'@I^&@>#A4;P'V_(_.\LZY=_YW7YIXO16.>\#T% 5%P3Y30DB-PQIS1[
MTW!(MICD<I0UR=[53J:CJZ^K=?WWN=CV!?WW.WK4^D#L;#K:,)!F$FU;C5["
M[5PUQC_^L$0E2;D@07K@P3MO1#)6*"Z<06IZ<P/1OXWR*"ZFTZNOOOSR\^?/
M9W^Y\>!L-/[X)2.$?SG&K[]<7ONF^NMR\!5"-.YC'+[]_7V.V?:#64#H[@\K
M;R<7=>)[_4N\[;-Z5O/S\BEW5=/=]+P;[+C%A>=P(-^) ^$Y0F"#POGP35GA
M;$$*-)5-*")@=95WV9LMRN)68MJ%!,4I"P'@VM7EY*BUX)TQCDKAM*%&,16"
M[9(08"<G!))V42EKI4P:"999YX5,U D@GEO?FA!8)]OYJWV0T4E@2D8PAKDH
MD'*%D!0 #+<T>[Z>GR!'=.2<!$JDR.VLJ(E&(,,XRJ7TS#8DR*&=S\D??YO;
M&>^SF?'3R-><.F\CU=@GO/--K,2-JT@^["J29[+!4[0FG)L [+%[6B$%#_)-
MG^T$-8)'J 8]A)OI15T0)_33TE9<O75R,1I/WT[C^!+_6B:(+52*!OG0+;5B
M@X=GRUWR.6K%)GMVRUVL6)>'42TVV'I;[N+/4BTV.**VW*5.6K6P-+?U"8HK
M"YPPS6*TC 8O''')\2ZI%OSD5(LHA(@H9:UE"KR.6C.A)4H"%!)).+87^_(A
M2=!IXW*#NV_+7?I94F"#0;OE+BA2X#!28(.QM^4N\2PIL,&QN>4N<\I2@&L)
MS@0;024(:%FBE6#1X&1:<0/<=TD*P,E) :F23(F87*X(. .D&Q=4BH3[2%TP
M>S0P';[8F4B)!@I$2".)YFCL@O "J(TM&9@Q"J.8]Q9G@R2$]B9*.9L(BSX0
MSNR)&9B[5;1]K'7)SYI:I3_.N'S$?A;C\AXR[X#G[%D1"YL,VBUWO>Z8A0.J
M%3M%'&1#;W<R9#L%5C!ZRFJ% \% 1.M25$!CT-8DR[WEP6M&D^B26B%.3JU(
MQ#NEK>:.4U#2:.U]"E2:&$+ ;_9B7(Y02HRK+$;K?O!U^&'W34NV4_ *>U;P
MRB9S=LM=)7SE0#)@I_@5^JP %K93  L[Z0"6P))D+GFJC 4OH]7$.N.B=A:G
MEV*79( \.1F ^&UBM@>H#V" 6!^T8<Y1;XVE(NW1M.2@K%>:19L<V"BL$PY'
M0+W3(*GS+9F67#F*-B5U3"EPR!F*)::XT,B6EJ6-2<,=-2WW?G8IR%E3C=_'
MF9>/V--B7MY#YUTP_5DA49M,VH?O8NW$1!75XC$+_0R"VBG B9UT@!/3D4H&
MP1@6 ='&2:4H=9R09&ARG5(2U,DI"8E1,"(Q[;5"%<$8 Q()*?),JRZT9B@V
M* E6T9A?0D/,8P '@6B2(!(5J="L)25!"*&D<)8Q@DJ"\D:@MLFXQ[_ I+BQ
M&%1'E83]^I\I/$-#>,2&%@WA'C3O NCWG,'W(7AWN&!SN%@7^"UF"[&=0FG8
MO:2N^W->TS"X?'Y2UN*#_+ZOJOX47^9Q:;X=#6L,S^+TEYRBM9=5VBGB@=US
M$9T49>S3P=4&/;SYYMUL7#TLE++Q=HO9/Z)H&2,F_89F7=VM(?P:QQZ_L!]7
M\[!!</P?.)ZH!&XC*I%@$S/1>P52A4V'I.LO6UB1-]3Y/@[[HW%-HG3QVB91
MP5=%!;N1%&_9PZ*BNB<HKN;OJ.9YBQ<V5+9**.QRHO0LYJZ-6P1Z/=1?[74M
MTQ],7"<ZA"B<5L0ET#;H)"3C)"O;47C64$SC60O60A&.-L2STOQ,W5OV&Z%J
MI]7[>#6M7U=QTJORM,^JOZ/HC%D^]H>Q%J3K>Y*32><[YFQ.)\4'_6,VRKFD
MB*=_QFEU->Y[_!;'E>^>Q/G5O9R"[E%HCV-5S[-BU>6*0E.YZ.UL,G_C_/EA
ME'^IIF-4,*MQ_#@;V/'@^NPA4VU5RMYC_F4!A%]P,W&,=XCIISB9Q/@.B1(?
M-OSX$XXM3C(._6TP\G^^N86E(+SVR'F,: T(1S:'OZ-&K$!$"$DTT1(E=#I:
M4M6;*N+V7648&L]B$VY;+R!Y+D'E4R^ED7IYT,CCT1FC7:#[A.U;2?8Y9D,G
MUQ\8! 0S<3:O%U#=+%(U7Z6U';E=X >@??L$=UB5>P'571)FVP>_PXQYYP4@
M@LD@TT@-[;X_Z$^O*QO^Q]; /QW5:()/FN&7T]FXSF1?7C:]0("Z0,4?;;;L
MYQR-KVN5?Y12/V>LYUH6\XL^QZI&CE$UF5U=H7K_P&-K?)L/:7K1GRP>,\-)
MCW&,N&YO?;;C:CNQ&MT0^OR.VK:PN*L(S6AK5;45$8?9(Y%-B_\[0\1DA-%Z
MG'C=Z*HF AP8KBQ>5X/;_%$9'F=7^:MF&9<[,BTP*3,9ON%\/$8+>8Z6=V *
M&0XQ_%UZ5[]O\F'T??VZ^LO5U@H<500A@@7'0$FBA?8I$50B) 7&&V.KUI#K
MCU_'>4FFU[^BL3M%JS9;M%=Y1'^[_G!]%6NA]J[>'_SRIYM]>Y\7^7RQ[1]&
M/Z_NS ^+C6D0>SFQXE;L_?C+#S=RCZS)O;>3Z+/L^SP:ATD<OOEF^GET3^S]
MV__ZZYQ\_601\%L<QL]V\ %W>K40#E4\.H6J!#!41YUA5*<H/24$_Q$-7H*#
MK=_==0FS\<VZI/ZG^/8ZVO%=I*YP5/U1F#PD7'>&MD:W]K:;]AD7_5QHV[<L
M:'3;;KM)='C!;F0!,O)H*1!"Z.=E01A=0_0,G0CHDUP?:RXX,J+G]:O;N-]
M-B+G^9\^VD, .G\DH!\.RJ-)"2 EKV4$M/H,2S8[N)FA6G+>"$"[0GF-/N\7
M^Q$^C.IE7VT3]^/0MXG>2*_[16]M&!<6%\4: !49ZO' @26B(>E(TO/1^RE+
M]AS /LOM^FYYI2;G^ET5<D(<]-&&J\O\]!\L I26SF-$!/Q@Z1!M']@:W9?;
M;MIG*&O7)4&C[W/;3?NL9]6.))B3:*R=79DX$4]K<%T'9_MQ'&MBK+%U34@,
M\@G+G*[_-II,1\->];.=3*R_0$-@.IU['_KX$]D?5W 1*%%=1!O^,;-C?&\^
M3ZC1&UD.N:):?)R%3#[3F3/6?!Q^='F9CQ'JH62.61Q'5.>SC[A(]?6U@)A/
M:SH:_5F-O)]=(5-=Y^MNO2SS1]]PZ& N#EH67#;EB3P9*S-(ODO?XF9ET%VM
MC0T$B+/2<RL C+<$./5*!QN\ETEM@LMO5S#F>R3B?/948^1F-'PJQ/XP&M^$
MP?R?E<U] %LO<:P7;[ZAC-_#U/JKR2-E/5ZQHL*T))FL9(JB:+(D1P5P;[RR
M41!#(LGASXV^I>XN]2/$6*;;L^KWFNAOU_>&\WL+7AE''_$9V4/<N-(K*M;Z
M,O]:B\EWZ0=\("[Y*EE[M'N]YI[9X$ E[EPR@4M<4^\]7[J@'E*A.K[JTPN<
M]-N:J.^M>\*OJCKP>JY(+-VS2ZRK_;H+?*.B=@WKWIPS<,]079A6_<NK\>C3
M'!5MKD-8%Q*<^S0V..XW;M/Y\GZ<[X?Z\3_>/GWM>)Y+RY6,"<4?:)6LDXDK
M:CRO$P0VGGQT8*O:2/>ZWRMDZ<U?2I6\:OU\U#WGILD$H6HN+/"OZ4+">12[
M_=K_-LE1 ;$6E2.'@K_63R8+*73+D M9N90V]G(TPUW??$*S<:-_G#_AIWHH
M*&WJ@7P8U<$)M744W]T,8Y57%7,*0"K.%""W6J,51<O'6DB0E@4$7^BVL[/[
MQ<^7V][+F^@R*X=9YMH=>.]1>_%N^.&B/P[GPR'"\'ABQ]?O4L;3;U=TH^_L
M=.W,+43"C;0>8D!6#<9%HH4P$EQ"S&W$UQ>S9_0!5LW0FKEIFE<4,?5F2><>
MC@4NW]<Z,_KN;W]_Z*?IQ5/VEPL>9:ZJ9XF'I)33UEJA!9H@6FG;$$[]HO;W
M?N#3W?U->46?L+_]M,#PRQ@1CSU.V.98)S1/^G-81MLF#PJ?N@#DA;HTK2*:
M/M5DAO],T?;:B_'>&&&R[:8NAVCLVWAO3 O:=I/I\((MW+@7<9@]M#=! J'V
M+2U<L-D.K<UU_.BNT5K'S;X=I;?YM&Z>\%>#VOS;0=^Z?)+17PL>J+_+T0,Y
MH"_4 0&+:+Z: 6K3;%(SW=QA>N_6O?!"8]3\UD/M>U'S1SB@;B <CPLUKKL,
M7-P$Q4U'5\M0@,4GRTX#"RI8A%1LGH^OW3O/)[<ZYO\;)NX%ZM]__97]&-^Z
M<;1_OJU](%_9P6=[/<D/N1@O+YI/I^Z84)'<-6$M.'W1KF/Q&?FZNEC$0-2M
M2.\$JC<U7%A^M;JH;^X%HC2&A38'K.P80-&8([[U+OJF.4CF 7U^+B3Q@CI*
MORE@)GIAT*1.*>H$ ;5U9Q(C/GE#G1!6MA P$SFS&BCG/"E@(CDE?<P!Z3@E
M?*.[%S#3.50]KTVJ7+Y_4'LV%[$1=R!T@C@XSMBY*/T_J;X(^(L=+TRRVBVY
M4$,F__[5QL"<%J&PN?KAUKL>3(C>OIT[T, ^ZRW6--"9_*3=]W*G**2'2R5N
MWY8=]G(UC_E1:4$)&"4RU\JS ,IS*XE(5#MP3GKA_9NU7=L];FYK<M.:N&E*
M1GIB]ZFFEMF;&TXOA/+^*;6]]EK-$WRX>QE[\ENVMK+?NJ;[B+@\;XK0W7^?
MJ<8V[(?KM=YZG[S6R>4@W?,.WMM>ZW]MM8W]_2;VI@U-Z;=5*_+>F?'<JJP;
MB+2+0ZO=##O35O&%]DSL1$/$.^>U>93OTN^36#=*7/6#$JF#, 2$4\ )=<PS
MC?I22$XZ[>(&/V@K7LCF H#[E@^/HL . =@/]7^= ;!W=S!KU?%5-[TX)'#=
MK,VQ@:MQDTX?N/8RK:< UT\+ZKI>[2WMHHC>.4T<@)/">(X AG^$7*77;#JZ
M:06R5$-*VK$A:[%)AX2L[NM9?Z]MD1QS@W.P'_.QU:7M#V]Q*_OZV^:OW56K
M'6R^';:@I=(?#X:+K?/O<AO.Y[OPVW(3;F+VZ IC&Y7KH4E!C45]A 7'A55
MB&>.>OQL(V,WQ!'E>*TWW^BS^W%R^9O)_GFVZ!8M,&WH3WP=K)//PE^[:M&R
M7^$$M8$[:/+=@CIRO8%%!OMJGH12249/".$1I!.&&9(D4\%'*R/;%(WZ0+F
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M^J2*:$\\F) ;GW&A+5?":Y<< 6$\T?3--]\N>EVL%#384N%L@RMW\:#59 M
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MN4;B.7',7N72O8OZCYMBVI400AK!A L1&$<USANN4S161X.:70LQ[5D;9(8
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MQW:O9,9L*)I9I%J&\Z+,FBP+9AZXH'1-QRF/=<>+K=*9=WNLZK!-A31/MO&
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MVO71T.^(6CN!O/[X:W#*7MII,+^]+%DFOC&C+^9VEFYR.6V^5+W.-P6[_KU
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MKO+XI8'=@ 5=U"J#$(C=MM?_-!'I;A5RBT:8F P^W3",AI\K+<RR"*AYA8,
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MUA$]*!6P4ASY8&A@!GLC263!: GP9:38[D%U$FL).5"Z9Z<)._%N3I0)V[&
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M-^N< VGP)A!G<XYB*XEF$MO7=B9W][<&T!0Q!@$.'E*8O_Y6=3= D**L%P6
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M;HFSW2[,]AVUXPD1;8LK&73CPY]ILLCC)4Q9OI@M!<1^^O KGHM@0N3[<68
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MYAB,)M71=V"R@KS]+P L8KKV(UNB'FMB;W[^]$]=^P?@I,1_O0,+H! W >J
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M3]@DCDQSPDG>AI:W@I?H5(KA5'<M>/(D2Y[D%D+64["?F')?_O[Q\^\?SX6
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M#'1\P8(5\+HJ%S\MV9QK"^A.'N/3\"/_5'MSHS9ZIQ\YK)EFN_A0Q+$F49&
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M-B0V>R<V$]TTQEESZS%78*.K@7+_3+-P"6^Y%*GY_22=^<RQH\"T/#.T'3.
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MO9;#_T#HN5PG=(XD$8P+>JBQRX)S[%S9O;']].'BW<>S_SU[3#7W+8Z9W<C
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MNFF,L[8LX9QPOKO RT"WG''6ZB.<$\YWB7.WY[IASX+SX?)-QW01(_--'Q+
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MM^=$[3%%\1.*#P/%ONZ[Q!U.*-YO%%N^;@Y/F4@P)A@_#<:>;DSZ31<<7]W
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MS9UBO8!1B/F,HKHHN+K*;B8>N\,P4@54H[R5Q:DK<7JQ9]4,ITW<U@OH8(3
M)9A31=;<=6_T4LP[6_5,GJ2@U_!^Z+%I&.WOF]B95>76]D:V749\)N3MZV)=
M6Z0P=A9%A;R/C@%("Y:L2KZ>;I.(*.6L$+(Y:W<6V,&:.R3U27.!H^"MY.QV
MV=K-#98*$/G!L3;#<K8,9,$N^4E8</;EA"%;[7<LO6;+$E\R*YH?R>&(8#C-
M$)=1G8O4Y@)1?6:\UF;J\DS<6VW>P6[17<U7W4E]L:&*M@YB<)5U[QBCGT#\
M,[P6U\Z* H5BWEIC(QF*B-/X1YUQ=,*Y(N1 H)$+2<A!!*?)%3]!*F-0&E=Y
M>B4J0B69E'[X70)R>EGP3IC:;WEQR3+M4\6RE"^U#T5RA?[3'UGV1=?>,>59
M/5-1=4*G@LY9?ZJ))L)@.GAS+/JC_<3#HF;%4G@,3[7?A>Y'(6]^L]DA?;,S
MK;ID(*U_)O-Z+D)%[+7+BM5 U?M0MU[RC!?0[^N\$ HX8@M<>M0IB[S$B)&W
M==%HLVJ6%+$&VJI *FAX91O0(91,/I5[1B6.DMUP#9"J0L1Y"/7]TK0Z#N=Z
M-=QVPE%S8<04:$;X9[H$A!08EX)!7&N_?$QXT)9DVE[%YR,O 7>  ASE6W[%
MTWS1COHWEM53#% 4D_Z3#"]-1A>U)\0K%8B=2  T>Y!8G[ AW:IFL.'-\KH4
M\3N%"L!=:A^_8?/%Z[>K^%G$XLM)<.JT@5]XIEB]%1^>K\U-^VC2Z8M\C^F<
M&FOOF0J-I3K7[K[JB'-KGW ]MK>I2Y704HIAZ+! MFN>VBVR\?F7P2I:2^^$
MN>+Q[_W7&O__[;UI<]Q&EB[\5Q"^\][KGBC1M:"VZYF.H"C*YK0DJDEZ/#-?
M;B2 !(E6%< &JDBQ?_U[MMQ0*)*R2'?1JHF.,45B262>/'F6YSS'/AN&BLBR
MPH\;XKM&![.9 QR>;I^?!Y\4'PS[[DG>?L^+&BY#5<E=WXV]YR.@!1=<E0MK
M?V46'NPSS5//M8/H=7"_AZL\7%^"P&(4>OH2=S6S[I\Z3/'N[5@#3A0WO@L(
M;=%YOO9V&Z8F"UR1(&Q"^RQBT=]A,* ;,'+AR>9H02%Q"@^1XG6A%O38:SA9
MS+8LJWJ)9C?\S$]*UN EZ*;9-4@HZJF%LK-:E(S/)X.#S0VP#1<*SD !FY/N
MP$\M<3;14^'CF^;/0Y#"@:WE86LN+;AE-PM<@G5P)>'J]>=KC7[B&MVW6B_X
MM*QH,GVL.Q^XJKQS .1;=Z(VYB5N_*1"V3W"LQ@W=9GQJ#0[B>0X\B!@<6_4
M@AY$I_@5;/57>'S#?3>@"O@=<+/H9'J 0ITH6/^?JUOX[KIGQD$%&"!1F+'F
MTHK<VI]J 4]&7_0&5VA1?&(L+OW)S<YVC[9G+R<-7I3-JE[3"%%7N_>0J_RY
M:%;F4K+M&IVRKD3#L7&6(\S7E::1WFH[1_9VLPU@2/#[%&^$05U58&W1:B7L
M>=IWW\+A >_$M04M&]TH<*)!'%#15W6#CCL60EB5S74>S3J%)]MO-EO'H+?U
MC8*S 6X)SP)=WA1U5=J]B1?;V -5D?"H8/1P:'W2L)!B/\)Q]EMUMN]*,A#W
M:1"T@5OW()SV.W#85-/\^W=OSC^^?0=+=8%#^>YQH.#1I)_VA\/A9#J(XW&>
MJ2R=Y--1TA_-)X-1/^Z"Y\I'RBBGP^N.:!F%D9\R>]9Y<IU<'+\':Z(5[@O'
MI]:K:LOX.A;TZ>*1G0/^ZR^''RY.+@XO3O[S.#K\\":"7[PS_WYS<G[T[O3\
ME[/C\^CP]>DO%]'[P[._'%]$9R?G?VD%-C=#A[OHE],)@S86*/BJ89TNP2BT
MFX(MW'@E;K;H:5&5EZR"2<LIY[23CL87XRZGNWJ!FL:@H(3"NA4Y6^GVE?P7
MT7>D@.A0@-NO8 7A@D4!Y\/64T'.HU\.S@^B"RPM6]=LA6/)".L&IX%06<-A
M)V9+6H&_6ALC!N^AIW TCA4:J*H43A@^?D'15\X39DIH_IK5W37*. P6 ZKT
M+?X8C8V3K6OEAV#I8^1GKYK-'2GT\*RB&"F,>@$+#.M!402\,/PP>PIY5]#!
ME;''8Z_ PX-/1=;(H">:3U@WT12M]\/#0'PXC(QW@?E7-BJ5^C<TV$MT$DC(
M\ B!7X6G@\C<0728PFRC1D1Q@2,NT8M"8^4>.'L4X< "P2LMY^.*YIS#TR3&
M?C+)B3'[&V8.K.TI,TJ -0HYP,EVY3W9.B XK=Z3T;PQIB7-"<;8BX8<(]P7
M6S=0SYMG"L_";]"HL?_<F''S*/)U59[C"!Y<C%TS8I^T#$_T%5ENW4H+:SGA
MF\2J3.]<U1-K,=780D]S*<:#BJR 531[.%^7J3& ^3GX)UX;6(S2*9,,#?#:
M+\LCZ5^0 PP;W'\V]76?_KCEZ63/XRV@DK",#W6(?$-O\WU!X1S>Y23<[,6>
M_)UM-6:GQQV)*LRKUDWA<Q(MX@73F=P9&<L7:W3C^"ZSD<+I+3A5X TMG._>
MDZ[^__Y?GP\Q/T=3S?%.*L,J\KQ(X4O9XP&]FX)./(RN[JYQR<BP@!>Z.C >
MGR<L+1G)V/CV'!DN-,8S4#?HOH##5*T7&>D&DB6N<;-ZH5B");="JUIJ@ZE.
MB/RF0!6MM!QVIYXMC4<(_.62W#$Y??#\K< [PC)/.$ :&'4!'ZW*%6N9TH2)
M85> _-'RHR.(\Z)J+J(V;MO%\4_GQV].2!!^/?SO=R?_>79((L:5T!33_LS%
MWE>2%#3?DS^POT*902<K 0M@J3$NHX-252-/Y%5\RR;^?#8:J$D_255_%@_C
MV3P?S@9YK*=Y?Z9F<_T"3/SX!9GX1Z<?+LY.WYV3>?_Q[/3H^ U:]"_7?E\B
M20/:T5G1I NVL"@&5RU8UU,%>$:Q&S8D4&5JU""L#L"((*L,_U:4.0;'R/P4
M\\</O<HK2'>B8CLV>_\P7<FYU6"2'=D2ZHS2QOCRAC+(S7J)QOP_)'_,EPM'
MA&B#%7RNU;5HZ8*.XTP6_O7\^$B.4'C#>B&D&#A@,<SI$\B,\[^CH+SU>KEF
M!4C''QABZQ*DT0MDL97*23 7^<"_'%T5.H=O!=.0C*U3/&XHT)7)W]Y:G2Y_
MHUR^NH:O!],.ST&R'+$DF;X1]'$&'\?PB5I?*C)ZW52[I63;GE:+WJ=OU&)M
MC(M'K+CAK; I$SS4MES<0[P$3!I&YZY@I+>:XD,B*41 0E8$+B9:#2:X*!%Z
MX>O0R/\!+@Q&X!B# 2]-X/Q;K_P_P5&B4IB\&Q-?PA?AM\O@HHHL;HR_[9I%
M>VBC7\L*C7N=<OC2T4'DL# @#)0%QCE0U@.E6%M 7I*B(\EV%^R#)OHK)T'A
M>6>T0]"(> O"#&]_]5>FG0 _NZ#,%2ZG$0G/8]1DR\'4E1*I,_,K0F2-0?,=
M#PL2"72&@4O>CV>T_P8C]6HP_E[_B:X>C#/YE\N\GCM/+5 62%HP'\6\3S@9
MW?-N:];7&-UO3+++TKFP35-<!\-_TJU[$+WFO""K.#>[O=_Z1)Q3H92A+?C(
MK7NK:V\IM^9&A,.&S=!$ZY)13\X^])PC#CF0N;AP[ZUJ^AM'P#GXRP--R<;U
MG@5"*6[HYE-<5AUU7<<X7RQ :+0'"/TN@4A*Q^@:3V[F/ DU&YU<#\KRC?9]
M8>=+\\YC+%YF/#R*82K*1)/"-@ 4:TS0IC)>G95^U%684*L#FBI,$B&@I-J\
MH?>%H^6\6%5FZY2!*7 N>)/1K2=IBGYG57F!D^2-+"OXP"]0-D!6GF_15GH'
ME^UK-M4S^#H?#\\NHI.3B*SFX8_1Z<7/QV?1R8>WIV?O#R].3C]\Q7C_ )YW
MDN6C69+,X<"-X_X\G@_[<3:(AVJ2CJ=Z_!(\[\&3>-YN39_9^7YW_-/A._:Z
MC]^<?/CI.=WN9X+M8%GK"EV[!4PI#/)K]OP?8 _U^W$^ZB?I9#Q6<3Q2\]E@
M-%+C4:IU/$W&Z=/MH2?.))A:#[;LGN[)]^S50T< ^8+V+&:WH[>'1Q>G9R\S
M2M8%M$/4&F9>&:G"F1KGJ18EXIDQOD399?![$<-$2.>B^700_7>UQD0S.D?$
M_TH5-6!6Y&NT'4+Z.3\2I1)TV2F/2WE#<,G3NDC0^==P.0:)+@7>8XPX]LK\
MAZ 5HHP;3I8AVQ]D_<BW\%W7ZP2^%0R5!>&C"V=0BQ5E<6_12>YG.]SH);])
M:#[DMD53K!?<*TYB$MA;5PI-> [*A<DI!_KA&&!7@JKKB11%R;#D2'OV7 >!
MY*I6A@LKM4!<;VWYX9E.$5K%([R#Y5RBS$<4VZ1BGMHB!N_"/#V9YF)?UI\,
MQ2T2-#8XV.83C *?0C\&WC3(!]9$N2S(C<U\.W+.X+;"A UD60^IOJLC+O07
M"QZ@D!-C^RU=R&A 'OCLMQQ5S\@6=T:R==A!%GQ2E2#61Y@RPO4Y_)1J15$.
M=:W!.4F;Z+5(W]?!UY_#*N,=)!G4K((G4@ T)0))\L P/XF#]QVP\X\G'\X.
M_^>PMR4YYT$1G+_""+F5-G!.BN1(ODUXJ3DP>5U7>;'Z6FOE.6RI8QAX5.3A
MQ'"*GUF:_R&5>CRA,%5?,FN<@&>\H@]VM+5Y]$K22I0/0/@]NLL68TIE*:]0
M$]PAT!SW)*^DT:#>F!OS-)CP=8-G 0(^FM4K+X2'L%65ZX.(OOOV2O,PWKXY
MQ*4SJ=5:7V*NHD*(DN.J=C/"*K[F$@,!^QIL@1L0SAI^EZY1\1;_D!AF5K%N
M,465F-&F0ZCU/<CS#5[RRDX(*3ZCT"W&V#Q&IIE/0/^UVL?+VL?OFAPZ!BL&
MJF&<Q!Z'!I%Z2W%6 0\WF!P)IRQ(:?=0K"E87Y("( O"'NL>>LRE?Z0J,]5R
M'YX.M=#UMC3'"D7GUI7&(H!#V-.W#4P9[-!!=%[ 1"$J@"74IEP*V (%8YXQ
M'>$&R;"NS<U@#U.,IVCO S G H_)-L?.T6:Y060+GE.4)C%$170++%XR@_XD
M)3Z_27.N2S 6JCK;1>UW06D98UO*F<$*AJ:B8^$?_^&LZZ00647EFFP!1'!T
MXKOOI3'^!OS8V4"-TVRJ![,\3OOY;#I)P'^=]R<C-=+31\2"2"2^N]^W&\Q^
MEW@1>K?SR73>II#8&4?SNS^3@KB6>LP4C'^W [P>#7QH-3_^%K_S#RZP@\%$
MS_HZF4_ZTSC-QO-T-$DQSS::J4$6C_8"^[0""^X?K$[17-D:EDPOJY*@>M('
MP;<H*9=K3S>Q+KW\/%R4WEF#<&7;QG@&)9?)%+4#_J$'#(XCE3=2#@(1![QA
MP,3'9-%^JW1ME7&>Z3A+XFPXB"?)*$G[27\TS%0*RGXRS_9;Y6FW"MF4!%9J
MXU!""4?I58(LXXB5PNHQ-F3)VP>W9R_0'8DK-4AGX\$L2\>36/5!H&?3)!Z.
M]"B?QKG*]P+]M +M%'D)LEQHKRU-5C6,W+N$9Y2;%ON/N!'V(KR)>L[F0YV,
M-5K<<99/YVBUS*?);##3$Y4D>Q%^:GN[6"98[T[FRW6U*+BD)0\*V3I#7@<O
M,NOSW9\MC(_#$E6.U6/M0Z@775_=-?"SPNH^$^NR/Z'%5:5<O24Q#PFT;X0.
MT0(TG#<F+"-A7YC7'^ V+-BFZC$79,, AX1Q,N9KV;48Q9,F7=]66!^D$"9K
M"L;);(W@T-<+TIXFF%%X159$+Q(EU6=,$BCF0..$1UTMDRJ]@TT$>EF1 %\N
MJJ6NUXNJU-=7&#JEBGL"5C>"N2W2*%E4E?"8U4C.!*9\L:IJ"C#C;\TP^-68
MJHB.'<R)^'3@T4Q\$)U+O0[!B\Z.WY\3[OVR5DM;&,8L*L2X1R:[[S/0-YJ:
M*W\*FNCTP\?#BXNST^A[%,BFJ%7YIYY<RYCAPT5YMU#+Z"/FW%1*^1&U@&\^
M*=,#^"OXT>O+*_<@.Q4%TG3 <88E_RI;%F5A?1D&HNI7% !V/%68X*J*#"-'
M7FJ#<F'MU9%Y>.+^E!M16J(16!0E[<1FM<YL!9\?!TL7)@IZC;BQA29D*Q-2
M(,%,@DPBG&6CL&^0 B"*/_L;A.T*$P>3&)B7)CI5:V83L2\Q;V8ZQDU1-V/<
M*IY.**E[J%;I%5;N\=Z!E_&CY&Z.TW)$MM27BKF #%Z7N# 2INW!".N*.%HD
M"4OE(_8;)978:"]<C[%_OQA7L.Q7S'WDQFEK*PO<XTLNE<.@]/J:<I:::M$R
M$-[42IJ#)(I1U4A5+M<F7NG%M2DAYC^*QRS7-!6/R(Z?(N>6+L6(,$:]T6ZS
M PL1\YN?PF*'N\,N**;9X 4.:5V4><V89V3FP//%*UJ^];.77&5)I16V8,>.
M&,;1%<,E_8:;5RY\A<G8&J3#Y5>XQ@3D0GOI"<,90^.\Q D@" %A&MQN=N>>
M'ZQH6GD+Z\(M[NX?N"?/O2V9"9NO].L #14-9< ['@:KO:!\T4;KU!>%(8_W
M&/+?(_=^J]N)T2A7Q8(9E/#@U;Y$][XB(8_I9)1ORIT5"18W^447)B5_\*\[
M9L]Q,VNV0="<U24QN&']8+V^Y ,.'(([HWP,8NFVJA>(Z$$4PAJT#RC&GD".
M"*320QI9//DQ<M.@C?(W!-$$5@E'?,I"HIM4X$<Y8K!DBJIU;5[42RR,IL"0
MN]$;+QO,7*D-QI$N,06ITZL29/E26/#\3Z6T+>:I^:SW[F]9Y/"1WWHZK#]0
M,S7.^H-9&JN1GL_F\]%(Q5D_2V?Y^!&\0WOW_(LB3)@USZ)%=6L8)L(HTCZ"
MM!E!&N@DF\9]%4^G\2!)9O$L5N/A/!X.IXG*!GL1?:8(4L9D#KFZJ6JJH F@
M(@P1$J:4#<#(7K0?E;#J)Y/Y)!W-QM,\CL?]V6S:'XWZX_E Q4.5[8.C3RS:
MZ%#NU>[C9%,G>C 8#=-I&H_B83(!@RT!:<W[X^E@GN7SO6P^K6R2KG40T@XA
M!8]G+Z>;%NQDD*5]U9_H?!8/YYF:I?-I/->S43H83*;['.ESR*E-D*X,B>^F
MO+[4=-(%Q1YM^/Y&&P?2#[P2-_EO#BI42).",8H*2:K+5][+=BTM="3DG8;I
MWD1;,#Y E,J%B04XE[Q@]*_G=PO;H?6^=4&_X)Q= 3_<EL).$1!=2Z6(1!K"
M,G;/X>\Y$#N%ZM42N>(:1!XSH!@?[SWX1INT#1BJB+Q>'41'7KJ&0IHNLBZ<
M:,I\O.4FRJMT3;%10S54<!+%$ WY$"\F0+$53 90O8!7&3;(6QAR1T2?*91;
M^/Z._.9CQ6_7).R](/!;B\I1;2^"##-B8MRVS*S'0F>1>%=K>*?'BTU:Z1;1
M&Y18,14*/1_V[VUV]]J "L6\%LGR:D:%N ='TEUKG0H^3]M$U4H*#]W(-G)8
M, 3D3F^%Q S(CW)?3.=-O3S>''I>UV;UB*!H+<>I>8RI&/2E")\77-0B96VO
M1BNFY@:U;1B47K(CP'Q086QO69#W#@5,\,@%)8*N3?8*Z;Q*GZP&J0TUXB)I
MNU^%.MJ0879L#*&]ITBN(QJN<8L)]X_3:C:/XW'J4^VE&]BN[1]F!2):7&2]
M1_$)I0D_*BDJ%S'=B+):YC7OI(NZRHJXM[N1JDN%=+2B0CW2.2)X,;_U[Y#R
M1O\MU\6UQN3I011@!O[G]-U/QQ_.WQ]&WU/FZ\:-D;+HI@S29:[Q/;#FBA)G
M-G&U0$ B,[G>5JX%"4:6Z6R!-_RIA\6867&-V?7OSWZ:S@<3_)U>9* ;EB!=
M3#]7U)FZ)F7!]<"<9>"G6(6+5[I<?N?0\9+C=8U0>.K6 ,J&JG2P QPRU5&Z
MM#&J&T;RG__]X<WA7X_?T9WTC_>'_W7/O-B/I[%1MQ44$5!]2LBP82MDR%*M
M(QPHEC1G1;6\J^#.JSNC+?"9Q[_0$QN$(D>#Z(HN5\N[154@(,XTHJ@6=Z7&
M3\+[8<2'/PWZO>CH[+]>@0<PHP?>K%<UXQJZ)E ^%G$,307:6:]PKV/Y'4,]
M]#)5B2X[)]_+U5!F=J'^#D9)L:S@S#U]?SX;CG#S+ ID887)_"_LYO7K?QZ_
M&@S[@_Z CT;SSV'7"TY./YR<O_KYXN+?X#3Z\]GG?_L!_PL"NZY1.Z%!C/D2
M>&.ZJ);50I[AT[@&SUM5.98WE[O&(O/65H.S:.'Q^AMM#%?:[1%J>R?% D2>
M$_-P[NQ:YFQS'DAEV'GHF8Q_6""YI@([4%]WO,SX<ZVOD+K[IET(B//0XH3D
M D33?DGW_"*9DI@B.?TH6IB2>.[L_G4S'VH2\](.!)]/.!(BG%ZH HS?4F,M
M)VH%,M=Q>YKBPNUEGJ3!_;>_7-/S0FIRA5ZT792;5&2CD45(/>.D2)>0-> 5
M8/E_F O&-1(^?'(+(JND_1FS>(]-9)SB%BW$@+ BLGF"F"TK*:S=$ 6_[XUW
M@G[C:4T]G,W&23*9#6>3N#\>SL%CB^=*C0>3^32.9_N@T-,&A3P3Q.Y\ZR:S
M9 N=R5<!//=Q^DU1'\]'$Y!U'8\GTUCE@R3KS]10#?1\-$T'^X+6IQ9U<ZY]
M"=1X+[<=M4VCZ2">J/YD/([C47\^&X_'PV'2'XR&\ZF:/H)0;"^W7ZNB*<9B
M2_&(WMN8)E^!A=^70G5+_# 9]I-8S4?9;!;W1WFBDM% ][-!/%*343+=2_S3
M2KQU1BGR)_KZ'NC]"\U7!7%MHAHR3D?/)QU2]]$.W9&WZ'&V6<>W-!3V1$PG
M!9'72'=DK]D,:ML85 "SYT8^-C*P*H2^:KTT3B[U'T5WN14-Y!![*;4$EES'
MCM=VDPR<]J#TP@:T>EW]+B2 CSD>^K0@D"UE"/AUY/G9U@R<;#)5_?95-&<=
M]BQ(D<Z$B/#MT;F+TZT4-4ZW7G)T8IO &=8\#M7CV-R'FNFVO<NP<HA#Y7=?
MNO0XIUFM;K=1<T1$S>6+B"N/<;=4I9<&$[*[=;,1F1"Z'^P9Y);<%,^UQ +;
MO*X7.>S@)PP>S ^>9N=9'#IE*!T9-C)%"I8#EB=?N6:Y&\$3:7WM\4_1@5KD
MK5[<<#W(S[)A:L86";^_K#9TUP&1QSDGZL/.&ZIZVSVE;FT3KV]P>_/+,DH+
MB"#JU/7]?O#H26O('HQ$O>PZD_&^SL0STYXA&D[M>$S+9,Z&;B 37A?5I9 !
MM+-G!A*PD3XS<KEKL5##=DIB2EDE(F@+81->X]=@!K!E%'_\QH=K]\48I0X>
MSYG58%Y=@G95?>-!S#A+A\-X, 1?(8MUWE?#>3I.L_$LT0.5)&KO+SRMOY"O
M):<3[&,;7Z=M;F1Y']'ID%>=CN-^GL_U(,.VADDRC_5 #T<@N!G\:B^O3XQF
MU_H3)XPXP]=AU+6$=A^8Z<X63?,L'V:Y&HSR. '].LMF>9*FX_EXC(0U>\%]
M8L'=GEQN64<O+ACSJXDM+.[$(786DFQ3SWEZ<,<RH.@Q\X7P1F&EZ7EE_8;Q
ME]+72R3#8/*?8BD.68"57)G1P@E8K9@<>L/TI?"$L7Q5L6C81R<LC+4"W0?\
MIJ]N8<]T^*?"O-^F&#52_ZY<*,364;1Z&$C080-DJ[-=,\=/[_4X#+;#TE_@
M]-THIK'@GE?-@;D8*2G Z(85-_U$PP=+LU ,O/AKVX V: (0=[@H(=P# 984
MV6.T!-)3P^F$V#'RH;SE1S/+TN^8!]B5W/299,VXU00#51;J[J6N&,?T+*>-
M#:*Y/?Z V^BMD*7F<2PH]R)WPM7BH#C1=S,>2V>NP8"_'7<-IP838+E6".!T
MC>KL'UI(9H2[Q)52+>_#&4N\FMQ2\7F1IWOI )14W<I-]E@C&OYN?!ARL&_M
MY&#6W/&A>& A@_MYB!=EYX@E+NZ5L>[)X/4BB%Q(-$-L/\6J\?L^\ IM()W:
M2T8E.%Y 8MMR2>["< IA&\44T5(R)D=?XVU!9(VH*,9>'407U2.^T>QHIM9?
M>&#>1MY4-+9@QDP(DXM(<+5;C)5AS\ ,!$T,?$Q*O!A$$W6YJ!(^4XEH;$4!
M=8PK.T'M7A)A:F)R,22;DM6HB4;-)Q$T]!T-\^5Q7/BJN)8)=^,3W'G!2-&_
M2;IF57.E #RV@I4L]3U "6[_X\B5<S P,&&@D6'M9,43ULX:M%,&J+LLB-].
M) H9U@'YD\BL6-PNG*";!66X8&NNJK1:/#2)@0PA]C[<&'9!*]..LUU*P)\+
M9R_:4=PBF)##6$.RSB3!],#!X WL!U]M1"&)&H^4H-TP$685B00*!B \-^;L
M#N#*58N8A?(-:;TN5KT(]AJ2E.$*]\PW>E1C79H7MF.#N;RGS.<\36L0WJ6E
M-"%E$<,!@U55FY*3A5J7L.O">?>(O"KJ(GI)VMYQGK'Y[1H@=<T+4HPI4'=K
M@O_2,>\9R@'WF\DXV?Y13$D7%HIU#-7/A\)(81]1>80G850IP1H$T\>>EF*R
MMXW)P;T&?^*L)K;.LO4(6"GA:VP[C6">BO6(DM_!I<1'(<]*]^AEXUFCL;VG
MW?RBYGA4\YJNM^RD@')/&K"M/:\+%D,3',>VL &=#FND2LXWK\(I$L EPGP:
M1O%0R4Q;L4MSN;"8"#M/;:DE:K6.D06L+^&O_S!8_PO>1C YE$+PF?,R.$8R
MS1+"I5D;1_F#2Q;1B<D-D==84W.I$9)T?04?:+*KE$I7C6P7WU[G<2 3*'W_
MQXNCL!G9UA&T#8%W"BM7#N%*F#-K"EIC&S>=D77:<86U:/W'9YU?""L+ZZD7
MN2U :?E>"V[6QWX_=0]@G *NAO&3I<NV1]]BIUGX SL+!E_ )J&&6\*%FDKM
M\I+:X]%7AWK#8Z1$1>$55VHP!JH[;=#_7N5G>TY:V6PG0V4E.L^[V;=RP740
MK]J9N9O/D^X0IL+/UY;45L]?KF1=+#)SJM"WT3_\0Z'CE E\*=\ZI\?YIUC!
MQ*C6).^U#;5>Y/4V:IIV#4O704<!G;P@LP]LXY4T!3 2>>=;\+1S<SC52)GT
MMAQX[DW;3FF)*$@<H;=Q"E+A*IM@V4%TCF\51E#>QL:#-_VP,L]E868OV=TA
MYDD(=$VS2]/F4N;<I)E-K(K@E W9\KTOZZM)L<!S?;WBKI#8*\;9?V6U)OY3
M4RMJ&E.BY8+'A"Y19!=:97P6T,9HM9#"Q#BL#1JL\&*\;4M/^5[T$49(L!B6
M9+[NE(<*#_-[SY.-!#X)&%"6(_:VHO+HUY4">3#;F(UF;M=>++>]F\AX&^H3
M6G)IL.%NP'K^HFZI H\SUY-VVSCUQ>)$)GN<R.\1D/+*^ZQUWD&+9CA*36DY
M[+*_$Y20N#B-]P07<Z$@\M%'7]4<#F\TIH9QGB78URG3&XFV)R6&[YP]PYS^
MS[<=0&U2M716+9&Y(0WJ L6R[KFSA2+IZ ])4H7[03IDG]^)E,B4ZY7K2"JP
M>U8Z\+!  ,+XB_0,WFC70&SC1+\JS[C6U?5"!_7@MU>5V(9YP9 =J<'G\GR+
MT[VNKFU-ZF8K1U,!"5KS"KRWU55*QH@?02(K(\$4@\0EWI-I4#O1[LFV\+8*
M/\R1L1C3G.\M,A-3R*CKMMDU-9V-Q0WN&WD"=94T9P._IN5X')GY13>CH>_D
M9@RN4:R%,A(4&0[::@DR@/0C&1P_DB#+$&)[@[P](%@ADI.PUTSC97J(<<*"
M;0+JEK1R_D0$(X>)4-R&DWD30 =G=WY)AH_T1).,F_[:"[ OMD2]K !A34<
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MJ?.'RUA%B3F>TRUB';H4&] D1F;0"NR<^GDKH",&].@65'*#R[6U'?!0VGS
MD^B!GD7Y-@Y,TGJ(14K=2,R=I3Q(=:[8WNR0\=Y62N9-WN<'S$V)@8B%;9K8
M[9H%VJ(3V* H%H/B/AO*T@R8+&UH&2$+O$.]R@95"<PS3C_K.(H9^%7@ 1.L
M1(%WSM1\$_9+(W?&&S?F^HL2PSHV*6_2F1@@K&KN<B9[A43'Q%4:/(RO8*U
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MC&"<XSY#FC"&PH_!%-6-6JR92QK[A1@#R+Z05 GF%VNM7Z&LX3.**C/-:^S
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MXI"8::8*NZ^ 3Y>+:A).05ZZ_GX_G?_%<+QQ5^:*:^O@?WZ F]&>;U^_>A?
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MQH[2!:+JV.6W.;'F;?7BXF<4/.NS[6H1IO=%%%4TH0+/,'\1OU4H& \<K74
MN53#4S>Q;+9?/S ^VMD=/@EWD<-?WXB8$]JG^%\8\0$X'#G#-(NZMKTQ!5T)
M^M'2__J*!#-^8I(=]P"224/U.D4S9@(Y>TDD@>%U"L*<"G 9%(_G0-=L?A!C
M*8'S%0L+V D9FW.,#R2N(JSU$M@C>B8+;[%[HF>@< SE>M!%1!"E:D='GS"6
M^'/#YF*R+[68O'R=3%YI,7E51R:!WI5\DWPB.R$EC/>8P.Y%T+\2076YZG4+
MKX?8!:=AS>_Q"CML*4L@5QU @)S"8IG*=6,PC%BE$L@*#R#]ES/I"=X*ZM6-
MK5N&N-V?WA..+0$CA3SIW%]*F 1GQ55KSIQ;Q));5T;:BZ7#UA@GK6VGH&Z$
MATEA^QG"#]D?^M,IL3!WY<P>H>HLA<]#1C99%O"%T\?]'&)P;4!)C[BI_=)3
MGELF=^8\;3S)G?)DBP6,5@0Y*8/;;E'=+'8TZ/2&YO^:0[9&C@R0$SQDUJ@;
M*]OM7-16AYFR>2JN6C?FPAXC+SC:=IK@:M:OU,8\OM-MLQLL,QJIC*ENHNDQ
MZB\=+(E 3MR/V$ *Q]&9Z5*U:^-ZBI9;(/#B\FC>/?;_WZ&F94&KMM*N?X%O
MEZ )<53V&Y&#-F1M9%+@C@=H[1]R9Z8%P2G'?F?';MC73=?%(BJ*TA"U$4&1
M6<1/E [);"[ZTZ\N5HR8"P;YUA\!YHT4-&!J(X<"4_ /JZ4MY21*ZN?4_*WA
MZ@Y<JBJ#M_J48*2@7MW8TMR.;09-QD*JBAAJMN*XG:"4T_W;:WJ"!9$^[V(W
M)1C3@:J;\K.(?V0<C^<H7 LJS70&7-W8EA/06Q9V)ZK!;/TYE&V5AU6/R!O5
M(R+8 T===HX4^.I*'.XKH1];.D"QZWZE$-XYY ]L?X*.L*_ 4E'6189%4=$A
M.)9WL1Y8B#[*N@BQP!##B:KM""M]<F109G0  0F-!RD:0+6;V?JZG')&19 D
M^*_FR%W@&^ZR*KR6*#E(_1\XVZPU*?5XKF +S$/EC? 200-X@+DZF@2H(WL5
M8Q,,!\%7MQTR68%G:MS95D]7V!"5LPY]E-,M<O>W%(/IT+6#%@-Y) U9:A\9
MD)26H[Q4@W6+ETK:3[K=F/+6;ZR6:?K3$%S?.+60U\YE%3 Y!E-RX9MTNQPL
MR;1MHMF)<U#4QNT5;E6NW+_,)2>./ 8G1:)N!SA@Y\U&7K>.6IW'OB48L"2/
M QU#A'GH?QPA_@-1#_J6/&(GN0QG@@XHQX(6ZB9*39]5W=O5)UH_OH]3/<B?
M+CV"DTO!7C>KJG(C5VE)E4'R6@22RHH)_]A2ZP]XPJ/.1$].>^!^U>+;">LE
MA^\.)+U2J'\DX:F<Z.)<\OAI].7PZ58"]8\C/,C5A6(JC$L//B 4M% W47;Z
MO<ZH.QQ^N4S((%E4-^+#)/>>>S/WSC]AZJQOL52.O9*!A9TR>9=;^U5/UFBL
M,A; UVR-L8>?Q8#)[2UR!QIQ,(2S% <3E5$5Y]=[-<&NMU"W%JU"TMV4V=J\
M2G5AM'##X>Z[T ..5X1YKK,&9MB,RF6%F#67 ZC-U$V! #J,$O>.\>2<0:*D
M;KXW<8:X^)1Q75E1.\CDW\B1^UP958>^75. XYMX0C8W9N&.;;5]?A"^705J
MWMV*M@>BF-=5H'_N].LW+#=/8=M<@1)G>+/@H4CK/U$9\XR +F(3Z& 10>@"
MUHWQW:&CC3B-.:*L"K5Q/$5#C!HKEB+4288><VO536DC=8!=[G=\P* 78C\P
M'FR ](.^Z$Z<XKJO1I7FE[NV:0[Z9C?I@A-%=?.]H6N(K:%OYX]2PO?,FG4+
MW=40_EDDC]'M%M1-)U6NQMYWHO '7=JX!P<:3 ;\<I3IAOP&ZB;(,%.!0,GQ
MU(SG[HH$^.'4)>N47>Y5D-0E,2KRZ;OQ15H"F%.G-F-70?Z3ON/(5ZQ\,3:(
MCB'^$/$KMG0!7XM U)S;HSD8I\_&14OJUK<KO2*T]_I2K=U=&+(\0F>W",7;
M64?IN#='UG;/JL4WL.R#I&XAT8:77==E6G."5ZG3M3EU:[=?*:2YAY_&B,\P
M$)L]#YU6J78<'20RN3QVZ)/20-U\0?IIU1'F*^"R[.'6W>IU8S+/>\OSJAG%
MD?C-W3XBL'O5Y#&05UCG>)D;*@_*;-K%EL=JH&8K1_XE0^JRK%M #^1\FV,:
M#"6=M+"Z-$24TWK<6"3/S&$</__JL].?/H +'<97R\I5?QULFH[#GN0@"KG?
M&%.(0CJ+)6>KQ#12%>#7DC7ZO$F6Y* 9Z=,[#_.&$8A_"Y [9NUG@6&\E84)
M4>V+KG8A39H%=+$0:G)127C,U#DGQ7ID^J!/QW/";9-2< #<!2/H3V4?49>C
M@()D&_=()$5XU+;J8IP%F6V:)#KRB1WDE!)(@5#U4+UBF96TG@<R%?,7LM2R
M;;T2J?LW5HWD!?PP'MPQOI1A$/Z,D?V[ASA()!FN:\#4+6:/D"Y7Q:1R[3$K
M=8^X/F@]F9>YIA_L,KY6[)CV?Y"\"7#,'A'UY",2G@QE'Y EKY%99TBB,IZZ
MB27=PVX><E/)4]K+!YIP,;9K\NS!(0[K7,OI"/_MPJ,<!DK!7S<+"B;HNYM%
M]C&[Q=EGCK/JU67(*%RO\:^X-1?R,;?^-+XB$QRDCUU2-I-[]\!+@-KE 7MW
M,\L9S54.BK4NHBPZQ*TNL%MO;[$.C:%/>U@HKA*[.31@@G[R,C=BQ[N)>@C2
M?ZKGM_\#4$L#!!0    ( $9]9D\%C# _)1,  %02 0 5    :6]N<RTR,#$Y
M,#DS,%]C86PN>&UL[5U9<^.X$7Y/5?Z#XGWV-9/,9J9V=LOGQ%7VR&5[=I.G
M%$U"$FHI0@%)V=I?'P \Q ,W*1'T;-76K&UV-[H;'QJ-^Z=?7I?A9 UP#%'T
M^>#TZ.1@ B(?!3":?SY(XT,O]B$\^.7GO_[EI[\='GX!$<!> H+)\V9R=?GE
M[&$&0T(:3^X?IN1',/EP].[HY.AD<HZ1%V 8S,'A(64F5+]_HO\\>S&8D$*C
M^--K##\?+))D]>GX^.7EY>CE_1'"\^-W)R>GQ_^^NWWT%V#I'<(H3KS(!P<3
M0O\I9G^\1;Z7,(TK[*_/."P$O#\NRQ)2T-\."[)#^J?#TW>'[T^/7N/@(%>1
M?M8HI"!_;='G-IU^_/CQF'TM28D@*!%=FDV\-YED_L,H! ]@-J'___9P4W+#
M&,:KA8>71SY:'M.OQ]-D ?#T.81SYJAXNJ(51ZKJ%A!]XTN0>#",+[S0?T<T
M8M*3S0I\/HCA<A6"XF\+#&:?#Z@ XJ#3CR<?WY]0]_Q@)/[8T@2N3"MM!9(L
M%;OV(/[5"U-P1\2E&"Q!E'113R[/4LF;: WBA(FJ_/@$EBN$/0S#S<UR1<H%
M00?%S<OH;LQCNEQZ>#.=5?[6CPE2R=T5OT!1@CT_N?.2%,.$E'.V)K*]YQ#,
M$(Z]$#P"GWZ!G;#>M41+0Q_A/((SZ'M1<N;[*(UH<[M'(?2)\',OAOY9%%S"
M,"6=QU>0W) ^9@EN41S? _Q(1($.)O=7MJ7QQ-$!B&(0D!]B4FY N\C'A/S+
MZF$ZN_#BQ76(7N)OD9<&D'RUL=.JF)V9A)8K#!:$!J[!UJ4[-E!9Z*[,S;L0
M\G6W%G++Z=.H<R^D:<7C H!D![:(Q%=-\$E:D(;,REOR>ZUH\)H (K94B!K2
MEXU,A4*)$/FU@D.:4B)<-SHOEV5F,R]^9ND9R8KGGK<ZILXX!F$2%W]A[CD\
M.<USR!_R/__W+(Z)'H5D$G]!^/F@_L<$)M3.XH_'0ZEZ#2/BJEO2NH*;B.2?
M<T@ZBTPK$CD;)N@1YZ:IB.LF5R!RANO6>]@O1),?:_AH9]$YQ7%,^W8J[9 H
ML2SX9Q@M6S6!# VKJ/IIDA%-$C11R4 X /CSP=_IB.L%P/DBR8=?@]4]R^ES
M#5%$$@-,0E*CRJ4TN4,$-"Y5L(X9@GH5L.;5^<&=ZLQTO.!6(_=;+09=\*MM
M&#CRC1 3M($H,&?_*&QJBC3LX" Q)VP \J*!QG^X@T8Z+(F([$V[&^%]RBVO
M?W*P[B2ZRVNMSIC7UWMWZJL<*5XC_-@8*3XGV]\$\<6.NXA IMP. J.;!^38
M,9:=P^O4'7C1D2H9E-/_7?TOA6MB!1G^G"47'L8;,GIGTV$-4!GQY([4Y'$0
M0#;6RF&C*3$'RXE#8,GGL7Z#R>(BC1,RZL\Z/!([^?''@*, B@Z'BS QME0!
M$AUY.43>*2 R;(YOF%&QP,K-HAP*F_<8K0!.-O<AG>N, MJ.5W3FJ)U5Z9#F
MWI"3NE2G!D8)JE@N01/8>ZSQ2S #!([!D_>:&7$+O6<8LOZ=J"P<J!OSY6XS
MX',)&+;F"E!B(,Z]H59%5P+PQP3YOR]02+2,*=B330,INN2YQ]3D+A@NME%L
MCAN:\Q,:,4';CN&G;JZ6JQ!M '@ (9V.5UJG39\;JT$_7'"2:(_,3:T%J#8U
M#58:(MW+9/*%VOC>V]"1K& :04I4S!8(B%Q%@)91&M4NDC..\5MATT9_ "=B
MD8S@VBRNHL+"8 V,Z$EU<.W"]W&JT7$HZ;8Q0D3G*B!T3=.+%")1[@UX;E$T
M?P)X2:<RV6S5"B9>R#;N5?8;"K(D&]XB@3+C=14V75R@ 25#\>X-CO*VD.T=
M(L,[1601T]4C"X_.58CHFJ8?67BB-/<W#.266I.Q#;&L08PBVY;F <(Y)$,N
MG3S,C?DC 1#L[)6A0UNB>_TP47T-<$)W+=%@+P.)G&X+"Q&=BT#0LDE1]2(9
M?:[VM[=ETK^4652E4Q;6H!9M(TL2T#I7DR:V2<.\7(Y[F_D*A6^1%\77Q$7G
M'CM[Q*MX+DVCPALTSE:TS!:="F[P:PZ-!W* ?+X>R>:]1;[@BFPD.BYF.&VE
M25(:I@$["8)9Q20)AL]I0B?+GA!MO;1S1B%197X3)0"#N!D9^Q6:>[XOH8.Y
M^@Y&"#.UN4X3?<[-;W\>KBGU7+](:7RMU?53.FV;[5+'T$"5C4W9<(:=1TB7
M*5MP81MP!2>3OH)D.B,#X_;L@@WW=L[!C-NE%M:8B>C@!D5CRN<GS IP<"-N
M$$!JHA?>>S"XB?(I-V+)$D7,ZB:VM!D*.&DP.(L@4V-U0*,AT[WQ^@,]PQJ!
MX,K#$;V1H0+]2S"#/FSVT_H,N>MT&%S%B;&Q&CC1D>G>P+ "8^XF:\'G<A:G
M^=G5&E<8HE&_;0F:6=6X4UAE'K:C))97KN9>!E>'WSL9/QJ/W/O20M'G_73<
MK(M;\OL^CWVKSM$/%7)K=TXTXBWW6U[3C6]#[CJ?P82C?/O#=D=Y^6' (X?Y
MJN35ZXIBY1Q$I%MNGSZ44I4'$054PP4BCO.1KCFU&+(5E!U,% C@=7Z'0Q\J
M+5H'G;&EBVTP2DG,VC;^<WK3#:BL3S>G2DC4K$O)(N0=2!8HJ-REPT7-7DNN
M(7%/)0][^)MT1*BXN2M3.,=DHS+TB*N'PB7$PS7H(3"%#+U7"QQ[5+@\Z"Y1
M- ]0/[HSUMH:D*G*/_LNH*@<@6]1?'<@5?MI2&1RM7-O*K$PC1]%!5]+&#:^
M?H<0E/EG6/@U-./-.@V<JDWK09LSF)!0%%TWCV+ B;0XH8/NW.M-<T2?RXFT
MYN?^-O\\@!B0AK2X!&L0(G:ZE91T3P;'D:#M&W"4D\$:',/%"*'WD8VQM<;=
M%)U-!6N(=&_-X!&P*9[L5N>0:'P6+&$$XX0VL[4@VS9C*M9N-9G<1(R5R4K0
MZ$IU+Y&@UDQG7Q *V*PCP&OH@_@1A0$G",H)*^%01.@F)K1-4^) )LG!%0=9
M/XV4_5[-&QQ1A4/J(GA-8."$YH&$^B@%18+7W.5]]9I/L=/[ \A_07L32 <)
M92=L(<%9Y'3WAPZXK$IQ\,*;H6:+E%GZH%-$/.T<C*&RN?LA)I65ZP%[4LK!
M]5[^ AV2+'[5G%ECSR\@*MG<.ZI?4]=BQ[0U/V_)TV8?M!/0Z.H%.8(LI*O6
M[MQ:NU?>\C_@WJFF8H(-OAJ4VQU58LHA=XF)M+*("CU)4WO,]8BA PO4M[\:
M U"AZ'S/6[>2'=PE(+&IAS-".Y*NQOK(3@V)]M]?D]P1SJ/L\+R_><)>%),Q
M&34H"MAO&72_>#!B'1XF74HTOTPQ-1U@B )!#-YCB=6]!;LNT<GHU773Z?[K
M2C<JVFYGW8M%[DT-B\S^%F'@A? /$/P+A=2=A7W3:'MA>?>VW5<QB@;=O9CO
MJA7W7"M#-=WN9KAW++//O;UO!,5Z$SL[P)W%U) C+M<<O/1]^L%^,-/I!(2H
M4AR;16D_!CGD:Q^-9R<>B$,Q](E6^;,4]3]4*+,82BH,TUOF+D'V_W*=AORP
M\*(Y>""67\UFP&\-T 8IO/+^R#X+'W+BF&I/0M@:$A2?;[[%]%ZX:QAYD4^7
MTTB*N^9=S6W.N)TJUF8<LGOU 0C8JL=-'*?T6<KIC#TZ2]HEB2:D=DE5D_A$
ME_[IG\\]UJ:7=.F;10KZ4D%<QBMVF&NZ8@LO[1Y[]V5MDX!=EC7HG+XI'-%^
M7=]<'-!4-T\P=JFF>Z-1OL$7PKL3M.FES>#"C9L3^H2RV 6]P_&"<\_"J4.;
M)N^]S3+KQ]E1_R=$TDFZ@V21C0GIFVS<EM.$6D<Q!0*MQ8P.F/TXK M>K34H
M8.S2LL@#6.7V3&?5:YU;N]3D9.56-!'9V'"F:7 ''(E+*'"BW.BXUW'_, ,H
MU&%L4)\EV*O^^0X-;;W=NR%&H'VV4<MB*"=AE _EN(Q.Y)+TU56"FCLOH;.^
MF^E,_"2K),.TD,+).XVD.!>,9>! ?;E+)U9S%&GFJ$8*]'G:1W#.J\A'GM"9
M3R(6!K?09QOFB9*55\$%B:<F5R//5'*-#F%6[NB"*-T">8]G#)PSMG27/T6M
M0IX>MPB!*N[1(]'(/7TB4E6P@YN\6C8('WI5@5+)*,*CA''T4-1U2I\HE)2I
M>Q[LNQXFJ?-N-X=)7+W=FUL6:%\>03(=)DD8Y<,D+N-P]Q4OZ8KZ'PQ4TQGM
M+RYAS%ZJO,=@"=-EPQO:],5MQ6IZYZ*MK&J1N0MT@BRG2':WL;HH!U^#I GQ
MS7+E04S#_\7"P_-6JY(3%> 1$(T.,3K&=H&)0+Z#RS%U1)=3;.P,N334\$FY
M4:9).CJXZ!O>6VQIEN+>4Y!:RW1::TJC66)3X*2W!30!0A3+8_]T!QMCW19K
M5^_:1YD-ZMKM<\[-D4HVZHA(:>U\78MV>SNKC'9LP# QO0-6%,446<<'A^:;
MVBJ?^2R/CN^]#9TZ4X)(0"\$4HM^_&"2NZ!70+6**D#E4*=33Z!NHL2+YO3]
M4.XRCAXQ-YUM$X\-2D;&]Y;2MLMQ;U:JC7S>+4=,?V6$4G(*8Y6$<VQ0LW=+
MK_%+4F@1R5Q:*-0SH'P*VPJ*+6XC.%:XWR8D1>[9.2PK!1>;(!PZ\-BV@2VZ
M;RWF=;9F3$(<\IG&#S\-9_2*.GYY11S\T>DXR'2_6JY"M $@WTG,>:99#CPU
MOQR#,OXW D=M%_6/3%G1!4@_[G!?&'?T@U,0G$7T94* L1GDM+AEXU89]_CA
M9N*>OL>TLH*+SM>A:3>J,6"56U^'S-<@Z1:X?!TR%K^]U$W(]@UE*R%C@VLO
MSNHR@K8LW\$G+"[!"@,?\E:)>)]RW]4_C0T^$L,Z@*(NU;U+48IP6MYI*WU!
M4).ZQ(.">GP0,3&_$VH4!15 ZN4LC2"W*G6[I7WP RUC.B-JLT%(-<8U0&+,
MUWSS1LTW-N#8NJ0#A R*=/#*=^=VF*JW++JYPY2KMTO/&S_">01GT*<;G[.%
M*W9540A]HNJY%T.?)OTP3(F?:M=!$R^Q31:7]&WZ,![LQI_?F /)V&1-/#T'
M7]/E,\ T[6,J9S=.3-,D3KR(UEXC6%IRYY@SYNYYY$TS6"_,KS%@I=5OERJF
M!]@5!_<I)L"- =WDSAN(=Q96'9=W$#9<U+,% ^K9@[509JA4.7[OH(Q[SX=I
M6;3=\Y4?\#C#F 9JP:O*/0DT0;U"X-M%OHDG]X)^A4+N#10%CFAY@'79>IV<
MG%?>Q8EX1PGA+O[IBE;#LEVZ%[(RBU8LSG(.K,\0CAL'.VT31D$J)#]#FJM$
M?GM")"20M)5>/$9<W9SK[2:EF.RUE=)?9JBK EU(A]$T O\!'N[L%H4T0_<(
MI0T77[KB _7MRUKDL=2.S9MWU:K/SK(CIL]F"8F>$7A:8)3.%T\OB"H;=T:W
MMEQ#G&O(_2X0;^K??6-?0[\]W,)BI"W1L="6" 4]M@,]R38M027Y^VD+1CX>
MI#6H-%1L6!XJ4WVDE8PW=(MU^;>AIS";?J?>KCSSD"T6T)-L<4*' :U="I;L
M@A:J9A]N4X<4H,*;T$S9M$*7&W>=6=>],B#I77%F6KXZS'!N-G/HQD*%O;Z?
M+E.V%>\+9N](%L^XT!63[/7:]@M#O<K4:]2Z,M\&L/MP:.^HMU3*O9E)6\/H
MDT9]-PFNS(Y-HB'S^VH2,H<.UB0:2O'F1 =[<KB25E9^? ++%<(>AN$FN^L$
M!*XEG5O'YR^OH[01A>Y1#*F/KHG^OWIAJC^(-):HS, ,)#H3&/6UOP5Q_+3P
MHJ<7$*[!':%>Q/U[7:N4SC6A*,6=<-H%KM)LNL]ZT!SJ:UL@S\<[:N[>91SV
MIE9-G&)ZES[ _3=)K5(Z-TE%*7\V2:-Z<*M)*C1W?_B@;VHE0>1<G]2[W,[-
MKB5WA#X_?5>'UJ[J0+.<SG6B+&>,P5#DK$XAT:Q&>@J*C4*ZA4:E!6\I.!:I
M66'TKAJJ9CF]#2.$Y?S94*UJQ,6&JK3 I0,497)U![PXS7:>#K^BR"ZJ*%6C
M9V!#1+5KMGL57?4V8S[=8+&1GMA)-EM47:^_PH9Y,I+<,C[)@,%$62-(RZYZ
MNQ8)I>V4+\R],P#YL:W&82TUQHWY*@]J:_(Y#A=;#^ACR*"$,4T*:6=)VFF.
M\UBQ>^E,"@Z-M\M$*?=>>_+ZD=W!^W":!0%05ZJ\\*QXPN:R-?EHRI97IS[;
M8.U45T6Z%>WI!5GZI<%MZ)Z2>[AF;@P U-4YM5"@*XI&!N-BW1NAZYKPE42C
MZMRL)3I%8@QAVA;S-O&J<-?.@=LNW[WTQZ017J,4=XBK57:+P)JQOTVD"MRS
ME]":E>O>#=-&W0/=A-ZERZ_RVW3Z&?_;!2?/0?OI^+."W9N0,&IB<-T%G55V
MF\#)V-\N-CGNV4_@9.6ZMTM=UP9VD*<C/+DR##':D/$V@2ISU,[1VBA<\43:
M?J==V!7;SR&<,WDQ?QKF@I3X[L^Y&%?F8@3*->Q74'$O'G3BM02;.*!GK'5+
M%XH?66+T+0KR&WE!</7J$]*S)?W-I.FH9.BT([&,<<&N#T?MIOL1%VY[BTW^
M@?[S3$KZ^?]02P,$%     @ 1GUF3V>.*/RS3   2Z(% !4   !I;VYS+3(P
M,3DP.3,P7V1E9BYX;6SM?5MSZ[BQ[ONI.O]AG=G/,^N623*IS-XEWR;>\;)\
M;*_D9+^D: FRF*$(#4AY6?GU!Z!(BA=<&B0@0#*J<O$2&XUN] >PV6@T_OQ?
MKZODW0LB68S3G[_[^,.'[]ZA=(;G<?K\\W>;[/LHF\7Q=__UG__[?_WY_WS_
M_2\H123*T?S=T_;=Y<4OD_M%G%#2[-W=_93^B=[]_H=//WSXX<.[,X*C.8GG
MS^C[[UEC2O7KG]C_/$49>D<[3;,_O6;QS]\M\WS]I_?OOWW[]L.WSS]@\OS^
MTX</']__OR\W#[,E6D7?QVF61^D,??>.TO\I*WZ\P;,H+R1N-']](DG%X//[
MNB\A!?O7]Q79]^RG[S]^^O[SQQ]>L_EWI8CL,:"3BORU1U_J]/&GGWYZ7SRM
M22FC6,*ZH79!GW^LB9N$/Q;_FN??T4%^]VXWS 0GZ!XMWK'__WI_7;>+LSA;
M+R.R^F&&5^_9T_</Z'F%TOPZ76"R*H;T N51G&2TVX)7OEVCG[_+XM4Z0=5O
M2X(6/W]':3,Z:A]_^O#3YP]LS/Y#PNS],/'.<9)$3YA"+GY!$T*B]!FQ+K))
M.K^)9RC-*/@FSP3M?KU;Q/]&9(0&X_H[C)*W^"4B>9P=3LU>CX=1]![3N7XX
M+=O='4;%7[)?#Z=@L[/#J'<6;0\Y'=O='4C%&#^C,8OFN/X&*GE-7_$K]!B]
MHC'+"(_+0(&F^1*1Z5,2/Q?OC6RZ9GX&U?P&T==KQ?X\2F:?ADBJQ7ZH"ER>
M@Z05<!HHV%44D[]%R09]H>PV9(>C$>+)^0U&Y O*\H)5X\]'M%K3J4'B9'N]
M6M-^T7P47G7[&*_,PV:UBLAVNFC\9D8%*>?Q@I_C-"?1+/\2Y1L2Y[2?R0OE
M'3TEB+IW692@!S1C3^*1:\BX'@<J^A _I_$BGD5I/IG-\"9ET^T.)_&,,G^@
MM)31>D-F2SH![PA^)M%JC&,\HC<K"N9X5GRWS,_Q:DU?,<6J>/G*_ASC<1GH
MU(JZ1C]R!O9D0[&S*(MGU$^XB),-_2B_1?GNE7R#L^P.D0)9ME35ZMN&\J-?
MLSK<;2C EKXTQV3+7J9682GIR89BYU&V9/^]_&T3O]!E>^?,FGD!&NK8AMJW
MF$X ^@JC#CW]]3K-$:']7J>37V<HLJ4RK%,K5L99/EW0U]5\,Z/>"$[&N&9#
M>[*AV 5:($*]P'M$9\W&V@(JZL:.K7:N57:/9HA.#>I2V3.6N"L;JI7#1WO#
ME,KF*BKI::!B[!V:,62CC*Y.8U\!,FY#1[[GSSPR@QJ*#E>\#A.I&2[YP([,
MQ!&&BRU@9#**,%PX*;OQ7Z_#!>,PL;%LC9A'$+8V1*[^W[C0>\;FUM$QPDK9
M&5M)S:RAAUH]#[!NFHAFCPQCFUJT#2S79A=J8TNTB<5YY+)L9W4SOJJ97,T,
MK6(C%HMTSL)T<_I'1O6;LQR0!\IT!XKI@GUU7R7X6_8UC3;SF#X=MF ,Z,:6
M2D6\<DD_-A')6$ AW]K53=J?-;OAU9J@)5N*7] ^@&?9BLI.;:E;KK'TJ5T-
MN?V85.HL2EART,,2H7S?QUU$:/]+E-,E*3&F&*@O^\I9UF>P"A=XMF%FIT[-
M)7T!Y-N1/IZ<7U/(B,PJ.<L_FZ+666)QFK^?QZOW)<W[* %@0Y"75J6;L72Y
M'PMQ"VX&I*)_LP4!I]_/T2+:)+E!&3F\S4J,5U$,,/80@4O6)N0M6'V_0JLG
M1$P*V^9K0-(E%8K,-D_H^WH@#,K+Y=Z4FH(DW@7X;N@_6QVCUQS1):5>C)BX
MPQ<'2YT.7O7<R-!^DQ3B5 (E>-:2(F%YOYAP#5\8?1%E3X7E-]GWSU&T?L^6
MUO<HR;/JEV*Q_?[#QS+1]S_*G_]9O[ZIZNB:_EE_$=!O6)3\_)V8@-J5#0:/
MX+TK=6[BZ"E.BEP)BKV^;SEYRHHP?4=)W6:EZO!F[0'9 VY"VD-#EX*JCW)5
M&+C +0A>28V'!VN]E_Y/[_H=O,OQ.SAC3.BO90*^,]!<H*?\.J4B;791IMUF
MXCW5K%!O?D?73?8M^8PZL-%O6 ZA3D,OH3-8<S5X=%B7\/GD%#[@508\PXYN
M)3&X=@!6B\].S4T_XU<X+<2DK_ IV:&RB!A6"4 =NVNT*(<)U,)+).CKJH8$
MB&>)C=_Y@HU"K&RRR9>8Q/_>>Y!]3(@H^UCH4_J. 85N6K;O\RIM_J-?-K_.
MLHW:WFTJD:TKJN.P,U>G 3:N^)3V_;U?]IUN<G9&D9T551F90RJR=(OT.,PM
MUFZ S5O,2L/_P;%?5PI>9!>(/HM;#[N?Q.5#F^9LA#5AGII$;HAWUFY>&NJ/
MS%#YQS_-$IRA^<_?4><=[7[ U']_S2^3HM'/WV6[G7QO/O8FKW$WX"$FX'Z\
M[0AL6E@2%NQ8O&W3WF<:1Q>NQ0LV_4^Q77,/O]AOHQ6Z:,6BN:;LDW$-VB2S
MN@X+XN@[FTHLU[.K4+&F=?L,^Q9N,CH%.__SDV^6;N_QC#%U3[?AQF:L1D92
M^OMY[!?J.Z4OB.3Q$SO$EL:8W.(<91_+$,Z7E@M2^U#P)K4O!6GBR*=23E4\
M2&>QM?==[/PL".O^9/_S^\XP43?@UP/NF:C2"IP[A3WOZBCW2\KD_DP0L10]
M+E7I/_;RPT6AA=KK[3/PXNW(#@BQ#9;R,*G(B"JR>A45D7EI5*!6D"]1$2,O
M=A?J_-A]QEC'OA**<A"X%%Y:5:V+VJ!<'EYL'=SB%+>%*T$GF+E@^G)L /1>
M6EU73S4& !R]V##80_2*CA,[1!BG&RKSWN4Y8U4@4"-9_TN<8E*DU.QV1HNC
MODTNNUVS+RA?XCDG_;S$EH.>2^L=M&<O\>YN[-4SYZ"R>;&!4VM2+A%G**6C
MU%V+%50M;'.H/,:A2B<H9CA\O-C N2.8"L-QG/H/2HV;#[PTG%!RM:V:3;W8
M9FF54)GD.8F?-CF+0#]B?I6'KI,TM'WE-.FW]Q(38\<!X%3I]]#<'_(#83+T
MR)!Q#%8?9]':6C\YM=9E1%)66[E*[2DJ+G6L)J4IM1?0>&E%B#YJ:PJX5+&J
M#T[-^G<4/R]S-)^\4#_R&=UNV!A-%[W-?YZY![4MATVSK9?P&*._&C::W"LX
MN8U]=K%>UF-3K!,=*L%*45-Y"0:83OJK1<VG,K#;N*< E:64JDRL@:WE:X:X
MM9= &3<&@]<-,?\*6&Z#L/L Q,[UH3Y0[U-?2%%_YG,HO 2!6A?(YSV'1V5,
MU_'3W9=&&7CH&9+[M#9BYZFG!I3I #%>IWUE.+=!MZ(TN3!*W]WA A%7FUT*
M8B^MK*4A8 M,P:["@.O,:E;@\A>,Y\4Q041>XADJ"EUR=K#EA(T];!&AEW8'
M:P;;QQ:QJNP]--(G2.^Z1QFB0["\0"\HP>ORQ/<=E2X5K,@:+>H<$T ++VVK
MKRLD$P7 L[*VVZC; RIB@;N[LQ(JY62^HMJQ[5=6&(V/#[U&5485L)&7*!FD
M,2!1'\BVPHK;F%\W!T>1P:3(7/+4T@HM]#.5]AE*;D-[97I<M5_,TBO^'N?+
M\TV64Z>#7+[.D@W[ IQD5.@,S1^CU]YK83"'=BJB'@<O83)^+, )C7I]5&!S
M&_@+I[+ I[(^?7)V+"LC><.D]%]=<]*?_EF6MI^2TEGE',:2D>PWZSDDGA[(
M N@C/Y+%9V C'5G'A,TO#NX)'25=VY@\.G=GL:1&PW#EFI;E\6S8E\?K>(W<
M.ZODWLR\@UB#[2P]BZ5M:9O'L5;T[3Z+HT1P](K_N'%DO?W8D?^DGF]8J0S'
M0GU^U4'U-I^1\U 12V%W2^T_[DM'[6M*NVS7%:_KAW--:8A;)P8SF)O/0#$[
M5&!<C>[6SA+Q<'=]>S_YG\D]WD8)*^#&A9>"JG*X152.X"!<$C!4HZ9UN]P*
M1US$Q8OS8B4>N1;E/FN_K3VVGDQZE<TZ;>U,J_V]#^F\V)R1SR\H>5V'4D7N
MH<TT=5294<VN?P3,IT/.>M7A#RF9K$*_\RA0+YQRE,>PJ;T)N_[D NW^_SKM
M#_H]=0>N,/D6D>[VZ,#6^R,K>JV]C)J.&P/0$1<]_EZ\\?LR4CUVH=T[3 JC
MZ1^X,,M46/)T&%,OP6EEQ(:44AW6K1?GX"6U%27%!X^@BN*HTHG<>HF.#[F'
MTS9:IVW<)E 6KC+']YR\1''"EH4%)EG$B@?--F17T7W^K\TN&Y3J,UT\1J_<
MQ61WO4''_@?JK9D):+,W+S%ZV#$&YB+:E,>+0^0B+:D_B.+G]'Q#J+"S[2.)
MTBR:%<JD\^)?27&J_A=J[.)8)8G91^P%'0KZED8DQO-J$(!SR4*/BOEDM,>C
MFE/VQGKXO#(JDQ<'^ L_=N?C-*4L"L#?HF_%D_[WOT:;YC>(NHV7"!VB+_ +
M0LW5BSH" EEW'K(F3 2-Y#CI-3HFH,@U'HR4'ELO"@+(8%V=G&;QT!7+L]PM
MEJ3_,3.2"V#1D7(Y)G1ICLFXA4G:CQ<E#J23A2^^SKHEYP!9Q$0<C@ES&F,Q
M<GD3]>%'X87]UU3VB"?S>:%GE-Q%\?PZ/8_6<1XEA09/70WNT6\;ZAOFJ,Q>
MV.E\CV;X>3=:Q73K(/-0W96FL]^=EY@_\"BK)XA]@?RH.]'0\QXE;*OT$=,O
M)98]SR+M=&6@WU^@)=P I_X<T.?D.[Q'CHT6<O7[\J-6QNXUQ.8:%748&L>P
M:.VUZ++P$G\&1@.Z=Z/;B1]%-+HE/W>+=G>3O(,QO4;E.$(;>8FC01JKD0-E
MZT>-CG!B"WQB:U>4XS@NTJI5V*46L%4*I^PMRCG&!:+M&IU/Z^G!+AT-Y2>\
M%)R\R"OJB,8]#22EJ2JO\6G<'?6"F1'#M./:F<>X*,?&9WC<YNX=C')K<-ZA
MKW$6EY[\&F9S \>_C%]\*CPNQGW>O^+4<1JZ?+)BM2I-JW*9=:XT]>K8AR :
MP[4IB+8..TAI?;6UCHH@NRL8>C&7)[/99K4IHANBO $^'G3;5=B M_,6)P-5
MAV$&SMR+I,Y[E%/)T;PJ&BLX="HCJL^2\HE\A0%(*9#-19R\R /=)=/QCP9R
M'E4G UN/?#6A1 &0X=KMO4@WY*?J<\T'(=W?'R8A]=6\&@J"S"WGU\^(\^H4
M890MKQ+\+=R4:GS&H9P-[AW!+S&UV-GV*S7#=5I?-CB9Y?'++GU9<)G?8 ;[
M Q+:#+R,BH\>"=!1"^TNO/A8$PB^*\$] F8 !G*821D<$\S@(S$89M(NO/@>
M% A^%:=1.AL!,P #.<RD#(X)9O"1& PS:1=>?#8RJ=E_F:_U$B6[' LJ83RC
MG@E[,$GG[1\:E/Q=S;HV)?UC&:7/Z)Z.V.5B@?KW7COIO I^'KAS+Z>&4PL
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M/>#<L&*_KWTA:9M]>0G10XZO&O"6I?'C<-I=M#5Q0'<LFSI':B@;/_%L9E0
M4!W<D1_'WOA3K9$D#EJ(.?32Q;1%[R> -/4<NJBU./IQZ?4]6I>@GBYN</K\
MB,CJ CUU76H569U)*R+STNY K2"7%XH8^7&M-7RW?G!.Q>!<"D^Q,5ASD[D3
MXZ_)-NN^/.+)[+=-3/:54MD[KU4IE;-X#&S=<5; K;V$T[@Q@+LF8/Y^W,C=
M?$\R*:F+_R7*F:#;Z4*L@L1/&<"%X[UH<?$3<$;&1,_3T>K'CVN^>_.&ZK-&
M)-^R;TIVD3U+2%COZAK(%S5E0]%Z)FGH)[*&:CY@%9.P'GO1N&"SJB?"[A8G
ME%67.!7;:KT52*^5" JB5L>! Y#. T @XNO'[=_PA&N8;RUIJ)T.[RER!FMN
M,OV]<R>Y2Q=H$>><FTGZ#_:.2OW 2_L*)0>Y$W73RCYN0[>M,I*L!B3]1DM0
MZ^*41SSN');-+GA%28UUX27Z#C":FL5'C0E1S0BW863X23;8&T_24/N<H:>8
M'*RYR7.%>_RXC3E?H#5!LYBWP<5[5(Y$^Y&75I9(K[9CNW%EJ:%Q8\'733OS
MKY,K.%FQ.XW^S;.+=KOJ?AYX.R\M.E1OP%TY<,X5%MS&@)LR31?7:1ZES_%3
M@KC?PS#BRC=1$'N)#"T- ?Z"@EV% ;?AVLEL1E Q]"UQ67H[WK J<NG\CJ!5
MO%EENR^N%>>(UC@F^VI.@YCXB243(P+ V,!N*NRYC=2VA:XWR\YQIEA]^*3<
MM:=+ZB=:X-KIKCM=9M6);<?7A;3ABI[R"K(E7*7FE]!S,<"E/P(@J/7410.7
M8P4)Q[>(@R\0 %T1<"R9;B;+_(NSU#X[+@S)7)[KU3J*"9/\G K[W LER(FJ
MB2T@\M*V((T 4UC IK*MVV#J!5H@=JJDSG(OCIQDZ RE5+-N7!1(70<(%-1>
MFEU/1T@80<&O H+;&&*W2D4C8%6=6N/'RO4;[H^/@!MZB93!FH,.G8!95_AQ
M&T/L2WS."B12"5E"]ODFRRGZ=SO%2@ I6PH1)&EY)!""ZCX$0Q+>%8C<IL7V
M16;?O2GMK;]W :(5 J5%>R30$.LW! PM;I7YW48T.:L>2R_9[YSP(IMZC<3O
M'FZC(T$&0.-![QPNVPHK;B.??6DGLUW4["[:<BZ1 M,+$=*C/Q)PR/4<@HL>
MQPH2;@.2 @!?KM8)WB)4'A*KJFM WBC ]O)%1=;^2""D-PZ#EQI9#U5A/,/9
MI5QPDPV:3])Y]>6F@QA0:]D2(VM])&C1&8.!RX^,?X44YX45 -ZWJ'C3P-9:
MWT6^%VD:-P:FOH_ZQ9A^Y_@BWW!59C]^SK\J\W>?G5V5F9&\85+ZKZXYZ4__
M_!+]"Y,*:+P[,<4$U<VW' )/;[]4ZB*_\I+7W$8U?I#A;J,5FBY:(G$O/%32
M5>F48CIW]UQ*#(;AJC6MVN=8Y$N*.1VO@7N7/KHW,>]FRX$VEEYIJ6EE W=9
M"GS[6_P2D3S.BM);:;&E&B637P0W( %HZ]*&4EI'SI1Z0F(]-9LV%3+?%3>4
M,ATYB07&/8OQ,TJI#\<UI^!IJ5GOJ<\FDZL"-E*/37_.'?"2JK.(_C9=W!&4
MT9=\*\/#>%\/\7,:+^(9.["Z"US%Z?,=3N)9XZ/:>*^<)$?C?5Q%,?E;E&S0
M%_K]LB'(;F_M!&F;(U<7W+/6QSE.Z$J!F3XO:$((J\-;C-XDG>].M[* ]S-!
MEL?T8??=T2B>;JTKSI2S/@FD4\]M[\6'13;@YCO!^XB?PM7[V)5FPO4_C64I
M<0UJ=\&(V1+--TE5'["0L3PN/OD6D7FS]!];J7;W V399K7[K;#"(S7L6=*O
M=F:'>36FAIF["J$!@80M#V?KXUTN4Q&P,2R+%_?RJ92JMC<*Y>XV9+:D%*R0
MAO&98: GX#09U=/QSQES VUX HT2S,[G.%\K;A1;32E],SJ);VN "JR>+BAD
MC)N7_?D;$F]>6GQ)';;BN'T_,*XBJZX7$)*Y#9(# (#!2JI!4@?1Q1R=15IY
M(G%#K6I"B='=1].5QA087!E4%S$6V=MY;-V Q7OQ9P]LS@NOCS.Z-,H^S.SV
M@NV37V<H>EPB$JW1)H]GF2@TJR:L#@M)"!UYCH )BC4T5-ES'[V5L>Q/Y ,&
M<AMASC*B<M!@I^4^.R%/R[UI!B5-1[!DW;/[JP2/'^E?630K/B3VU^J) E]V
M.ZG?!G8Z<1Y9R%C)^N+V#5(>";Z/LU_/MNQ_KZCDF*@B!@,X="(!6AR<K=-6
M489-C&=[\;<A;S-.H"6GG1U;HTKRP@;V.K"QKK@(4MB?%]9M<)AI8T.-IM_M
M) "C_=IYI!U,%PW].)$8*4UI,P&-TQB,1:!BV*A80W(=[A%(X<5F25_)B*\7
M_R-R6.OJRU*WM;NPD1Q(>.Q(-#'([:KX^-3MXNT!K!>J\15BO"B5:8Q)XU:F
M4&8ODJ7Y&;Y+K.."R  G@.>IY.3H(VSHRJ3P(O4&K@D]38%4?J!2D,-^1G$E
MNBQN'9Y?ISF^3K]0HRTIPP_L?-,O#W_5PNQ8]@H@#V=_.N@V-,26(#]<.B^6
MZ7L\6R(3JS2'T;!%NL7H=%"L/6R'7:);<C1S(GQ8H?\[2C<1V5*6?V!SJ#I8
M87BA!O4R>KU6]'(Z@#<[X,Y6;X60U9%:)[N,_31YRUMQG&3Y"Y1'<3)DO\W,
M]^R7.,7L$K_BE!7*^N>HJS/#*KKJZ+"8SHO;)^M;FHN+"J<+=M-<OA44(=1O
M*+LA6]#0T9*E-JCHQFS( +1.;HIZ$MZ@+>C!BP!05YOIMQ21;!FO[Q!A&V'1
M,SK;WD4$]:Z2'-!2,*FD+7W&T_ A  -*JPL[WQ#W:(;B=5XF46?7Z</F*8OG
M,7T/=B !H*RO7)=0^FQRN(I@$TM9CG2^[2P2O'UE*8U@XKO8W1TTL55[K%I3
MN%-^Q>]4\WJ]X>QJ<I]55RBUGSG=Q91;$\L5D9FYWD/L,'"6-5S+P4T5%CSM
M6LQ]&CC?'EBE0=-4+18M$SE/[=8R4F^;R)69>'MB4#M)][I4E@K9V*.\&M&4
M&9J"W>&GGW=]H%E6%\=ZH&YR1&+,>8%):;KUX-HT?K_0((J!7FP"1B/GXPBK
MEF)\3;,UFL6+&,VYJZB2KL[7%=*Y>_W)K8?AVG&+Q369[I)?A<S<3=ZQ9NZ]
M<=P;FO<"'6YIZ2M5W]8&7K+CK7V%"9I%6<Y]!\N).E;N$KDZ0Z^<IQBH6,NZ
M(JY-"W>Y.3W_)*TQ<X]>4+I![+;QYUU_KC<1+N(L>GXFZ+DZ!+"3L!<IJ.Y[
M I)7%SXIR9W%>4I16/":>PL*?UM!LU4= 02V<C1WP5;%0T>@.:=5O>WBA,!>
M[*14*;J_W; QG"[N$"GV']G&QU,2[Q3*)CG])D#KG7)5<ST<C>@ !KE!'1P_
M.L>/JV$@#Q+(AO-B>OV\?)TEFWEY20S]S_PQ>M6; S(.,)#S.1P_B@$C8QBF
M_![M)$M]7=,!2_.R=E&Q8?2R=[]*[,B)RD$0$1T! D#ZZ1I9Q+2?R7. =V@C
M6^F.Q#,TF<\+5;H>YU@VL*5"PN8(T&)HC PO&I)N2\0-O:!RG-?V@-81B7+$
M?^<.<]1@//5\,Q7/XP?FH-&SY(&I9"@A._0Z3#.+Y+BU<=R2> J 4XR(Y06P
M!M'02S4%(*H@O,]I+Z38)_[2_B.2I_T[#K0;5A<>:#0\ M0,'@==P.AT5&+%
M[:6: J5X25$04GE8T$6*E Y,-#34!8:<=0F%GT*A"!\*18!@,*#D@XQO*-[
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MO.!Y;>O><T^M*]<#8L\>!R]F<KT"G6VR.$59]K +F?#.3H)HNVX;G_8$7#?
M()ASW_B=>9&R6HK$KVS'>U8AI/W, Y]-:E$LUX;[5N<Q+,S:9N3%4@XV8[\H
MH1-#2ETT+4O"/#20+2W>CXG3.#O'!/&OQ^0_K9) ND]=%1+DSA^L$K]ECB:+
M(@FCV]2+R33Y%I$Y.WO(JT# >U;%M-K/CO<M*5-R]%NQP]R+E/]]WAF5>$W'
M,]H9:I]\=K;MYZ8Q1?;:I'.6&,0N-..OPA:[J)9R*UTXK%3 A2$^R%BVCJXW
MY2C>&E;Z]V+M.]*9T'=KCGDN<"LU''(RR"LY'&(Z>!,L:Z6 3L7U/Y1T5=:;
MF,Z58V=S-<7PD6EY%A9D*K+LQ+)XL?S>HRPG\2R7!62E-/7=9ER:$T489$0.
M@2Z!'%ZL8^W40,Z7C9B FY!Y[-\X2G5'?^CP>O#BP&E;,*&?IB+CPL*/+P>)
M<7NF!WT"]!GV+>R=+S_2SCTGT+FE>7[Q,%-+'5P]8]N+&C9V$1]0&F-RBW.4
M?2R3N%6;M<HF_1U;21-'GH-RJN)!.HNMW7ZAPUC[6V>L#+A>IPM,5NYO#BF\
MHJ>NWW7YROYT7^^L^C1 Y"6>(8&/F!02T+^FBWLTPU39?Q?'*F(\9_?<9S>B
M FEVN'<_*DUQ]RW^Q*_!!B.61X2<5V&S! QQ9 A0M\VL3)(8D>5*;]6QRLM7
M--OD\0MUX.G:A$CVB,@J3HM2\CME=P=-6N@:UK@J=Z'9^/30-VKX+*-15S8O
MON!+%<O3P;T1*%^CW?U*K4;51B:PT>F!=M!P608K5"8_\HGVD1(C(Z$X\VF^
MC_ZY4)-]'/;LJ$77X@ FL.V1V%&AF<_@[R%7^F&;T8\R5C-[?DF_T7+Z=<:)
M":O(]B$$ 9DO\6$+(,7@X1%$DLW)5(8J!+(X.[[)$XE_G$1)* &:^VBS$@8"
MJ"BCSB+&(GL[/[!KP.+]@T3N;<Z+.X\SNC3^/,SLX?3ON",DZ@DZ]""PF/51
MG G>%9VL4ZEORA<2QUT 4.XKVXDI3]MI@ _20?P&J3A>Q#T$$G+?*R!:.0;=
M^Q,0A(B!I/0J).PE@/!J9]L8)'KO83] P7,X3*!"ZG:,P84WZ9IL<9LN'J($
M98(-<L'SVMOL/7?DD,"F-U:K!+!Q<\>[Q\S.ULP]RA =A>4%>D$)7A>9%NG\
MC@HF2&V -]CG0"H;^&Y;;:6UC WA[L6L?D )Y?G\"TJIFYQ0&2?S%563;1ZR
MW9LR!,Z?\8/:UH<CM=KZCJ8Q0Z$%+,V._-BY4"4%BW*">P%RZ#D7,$/HF18
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M[1FV^SR)V>7"/D?D(;:U\.):7'NZUIQVC:;Y$I''990>>F8#Y; ^VY5RA!7
MH!V/:550:N;%-<;6]-]E95$WI_R)T7T\U/(@[=SVFB#H/"P$8RUV1+-?H,[(
MJYY=AY#8__R-#@4K?E HV)W0-EB/#A#Q6)_$9+0XVCZ%?WC">G%/]6"52A?@
M%TJ89]?I3JO.W<G%PXLH1_6^JJFY-J[WL=-Q:.]O>\8:L9E'DWJH/G[<%VXT
M1^(^SGZ](@@U[S6VF?,CZ\]&Q@^_O[<]G0?:Q:,)#-? CYO>C2K*,CU9/=2+
M^"6>HW1N>\K*^K,Q9?G]A2D[P"Z>3UF^!M64=9P>;U+1CF_Q-YQ0;DF<;VW/
M75#'-B:QHN,PF\=8RO-IK5"EFM\>I#(]J35^TEG(6*DS;E3*:D?-^6NIH].9
MKX>PA*7Y:4GT:CXZOBZJ/HRO'#'A30+RPF:&^/:*F8WF>] "9H:GE*71M3"#
MS$E:39@?1]8C<U:%PY2MQI;K&BG'X4MT::]JU7TFG,(NO$?E:+4?G1YH)*I;
M TJ[3R_.OTAO=)/>I.?/?8)<4V*%^$TC-QDT[>15;10-2_7*@7ATWQW,6-*"
M)G)SV:N7=OG;AGY 7J?LCHCX!;%N*=%'_K5Q$-HJ#T=.Z^B[1W+QFX9N/+LU
MKFV3<_)BWG$O:#S:6X,-OD%EREM[A78Z/8X3:7[>K:H;>O7Y9M5PR[ 7:^61
MSH1PR[#=X0RW#(=;A@>MIF_FEF'!%\<99IEBBXN8H!EMHT(1E+P<,C7YB6)*
M<YP. 2VU2/ZM9^J53+V&G3C2U*-Q\'7+J^)\G9NUO]*1R.X?OD+N1^?3\N])
M[]*>*-IT1LC!O>E=>;PH6%%6J[J+2+Y]I IGT:S8H#[;-I]P8C_Z#6MLPAN>
M7M1H\+!9"RGI2.0=9+G?R&("#@3=1VH&0 (#E&P"!MY%%Q%>Q5<&6+[W,>[0
M]KS(A"GC2X,.8\UO<4^I=,VDOK34C7;LTTBF(59H(+)0WW$]Z%<VO]RXG(C_
M1>VZ@+C<-B"-U#82L>G/ES^_[ZA_0__IXKIZY@_<H_6&S);4*[@C^)E$J^J>
M^DI8TR)=%V?H"Y?D'*=%S;8O4;XA<;Z=+B8OM&_FD"SH"$8)>D S]H1=*'4X
ML1XVJU5$J#2-WZKNW=T(4XGR%YS,J1'[]Y;6]\$H*>N[8"24[O:9*PA<8?+0
M@D"=/_N()RM,<E9>@95<H"YM+*I<:8A;M9<]EINS&Q34F,"F!ZM]HX)0@&(W
M>VS'7GBE72TNT%.^UZ0OO@*JT.8";*J;'Q<8-8=C!/K4/7D1@U:(/9MM5IO"
M4?F%X"S[FA(4)4R/7ZAASM@+%CU&KWH8U.,) R:4YU&C==# F8,PM'LO8N%#
M=;FA_S*-:R[/D;CN\#Q-7,L&[@"X[G3O1;A2[.2TM0)[L/QF2E>UV^RX  A4
MWXCSV>W!C[K,1:YPPT-^N8V9:]*-F2G(6CG7/#*_80%43P,&8HY^%/+EB-=^
MCP, P&\@@4*WP?&!0JKR2'AT>?M1QU4J*'LQ:@&EV0 $E%V#8P8*1V5C0-GQ
M]J+Z)T]0 #0 8#A&\YLU^.BZE((MFH[_V_%<)ND<Z!V,YE/=3S><C]\0,35
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MYX)!MUDY:O!FGD)DH-X0M,!9>_&N^/KP2%"4;<A6"14580T.,:&W< #J!@.
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M4")WKP"-^AZ6M-%).UGPX3J$GR65QM\5KB\V^)VI;"M;\\1MO7#$(-@2+8'
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M@.RT]^<A8W.0S7F!(,X.4_!$$NW!*@@E$/-B*UZ. 0%.(-OP7,8B>SL_/F/
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M)H;#P>.%H%F7'U+?(^L^6:_9+7NR^.OF,:(@O=SF[ %;MM;#3P(:#;H90=K
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M$B(;S [Z3QX0KJY.CV;N>!&]WW@(Y;9E'\E#+QZ&WTC*M)XPXL<PA<#A:\.
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M!#*)ZD]K+7JAQ41CORVN_A&MMO7KI4-Y2L(%;CQBVXZ^@/HF[KCJ8-Z?J7@
MGVML>N"%!.V,-4.T-=HU+QZ"JQW,$*M@R3VJG?P@BOHAHZF8$D2J59V)+S?K
M)TSX,_'YCOVE/9LS\25-><DK$")JG6NN_OD%;)(>:R[SZA$Q\ G"ZFA\6=NV
MS(=[#PT&02I!MH10$++*6W0>7NK+)\QR<^/,GTSJ+C3WS$-ZTI(S'#S@*E:7
M&RLN/N'6E;L.X:5,>T6Y;]^6K"_3']MH-JPJ#5*,Z]1:4[[G\):&.J&5YP/E
MU3^*$N,S7M_AE*- >@U:NJ1J (!K>0C8O9Z:T50,T' R;[_^\MLI64=Q$D#B
MU@0 L1VB(8_D;?OLTHD4 .7^G:S8';/L(D[P>8[7PWW;2LL!R3B68.P:^/9#
M*U$8/3[Q6[>(A&H+](W9H,(H&%*)1YK+)NF0B&@T:,3GC\!W ,0Y+UX1PR^/
M!18#HK0LP BR\^FE9N;'T&-%MU6;#7%Q)13X#\>-"WON#RV"^\Z8#_.>+S]@
M "VU!?XMD'#8@4)Y*9 "W!X/DG+<'!!A%.<WF/Y:RRA]Z=8SQ\^QN&;0:#,0
M16D;,&9(HOBI*-0!];BC\M,FT\X6=8W1-V8>3+VA@Q(NY30'4<1!27,^*Y7Q
M J!I73'=<E\Z(+42%O*W0"\8X/KU6\#?:K]'0-R27[@7UX/A$'] I?7ZX-=7
MU>JWPV/:)3X#X *;?4OS4]^ NUX$G'EJE_[6@XQS2J=1&^WL0F#)8C!DPA4>
MW310VXI7<((2^.SCBR /E6MS0K#K-AR00-T0C!RJ4'Y(HQE5CTQ:SCJ+JG<O
MDDHML 57;1!Q:6DRO"*ZJGSP::P7.01ZGZRB+(OO8[S\^%*_[FH;K3Y'^3:-
M\Y=3VODBR\JVNKBZ&DJ A2LX43 .[G'MR[HSFNIAYW[W.D54&[+-<\=/4;QB
MQ@?W)#VXB6CU1DG +@=QV]H9I7R-<4*+4'6,O0ITR+)W$Y/)P]JA?4=\,NFP
MFYH;'RQ+M[PT/&-^JME@6%N;0J*7<CUT6GZ%L<(J>Q1$8#%,U*"/<?1\>JJ^
M#9^^X+7J;E((:*NX:-SXW-)['J)G+"""]%F&\>!]@;,,X]VCMQ?L\+M,5+OJ
M&5>_B,K8$?]R]^ 5IE8X&34T',R;)Z#+R]/R0W.TB<V8=%DC;]<FD$X$[\ "
MJ[;T0KFABE9,I5'[ ?O2CI9%H11$/K F*&H@P39E85+V[J(\M31;I/&&+9=<
M"#:*:5IWM%MB#<(QH7_(0D8OE)IC<@]]Z5Y6YY4%M(%,%P$#CFD-$X]CPH9#
MDBEB!%4>U2?DOU0G9V:G6WQ\3RN(_\11^BE^ZH/>R8>DF-+PX2$5*J..4GKI
M]L(T=^KYG=\^XA1'[/,0.&T++44V-1II=8Y5NE.E7LW^3(5YKU6A=@^\ %Y<
M0\YV+VMA#Q)6+F:(.D$%/1!S@YB?MTX4@VIT'*9,7[NJ._V%%MNWW_'J"7\F
M2?[(+VKMW1@FUZ&;D;2F'WBR%"OH"(3H<%W/KS&[^[ND0D+N$0/3?LB($' 6
M2B(;?#LMZ7NTD1-^KR;DP^CI5]0)7V2P2L+,$2H]H=+5#P(!9&-?#-J'G%S4
M$)3%EKFXW]PP!S?-1]*:.N!D.;?7 0AYZ;B<'_UZ=+0?JC# CH4:\,;33@1J
M3S;D[_9B BB/GB[[P:%Q;)4>R]DI]? V\>^8!:$(L#=9SWYMUW%9=_05W<D7
M<SVLXW:7<&G6^[!'K'=<CH);LG59@YIDH7;2-5H?R[/.*[-[MB8+C7^(K =
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M#B7#J#**!9&/_061XO"MRW(AA"V,E LIS>*(9L4!Z7Q0?< X!Y-%B.YXK$H
MNZ>GF& !YW]B]I9"O#PX?J*%R4-G(;?0R_)\O<IK*-H(BGVN3D(C3B29$''X
M\@GW#8*CL8=*![)KXW*X5P%);M=TJ#Q#._<=SH=;$.T/Z96%4OBL#[F .EMO
M5N0%X^);75'E>62U(:4<>#4%$$FSM'**Y%F@'?HV>M'EWE<7]7:-KB['SFZN
MKL(69 C.&*@S$#C-E-HAJ(EL.W^WL(5AM#(.H)\3JH)^@5<'JBJ].A1BL5Y+
MO;=?\F)9">Z'OH11(YZ0%?U5";NK\H1;^Y&RXV3YA>),<+G])N'BJPE+0^@
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MWCM\CYA_5 ;XIPPU(6J\9C\D 1*Q^Z\)(<V)KL@J7KR4_ZN[5B9M(RB.!&V
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M6FRX;EUF5WX^I4OIY$,F0KWP1Y9 _5IX"9Q$TOB@?O06X<'Q8N'#-IB+AU!
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MRC[(RSL58$9DW_PM8UPRI0T'\@E.?)^#,*.?'MBL-_6I>G=/?O+>;GR!3-\
M$Z!"=0]'T"E1/@DN\VZO>AI4HD[M)'2@H.4E9((T_$2W#<-3P&Q"5-W@T-,
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MQ)QD<@8&G>7TK:4#<#[7UF<'O9D8>D$TA5)ECO F"0R \08:.O!Z$[OT=O7
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M(C.+EC@6E%RM:A6R2*AXOX=I(%3\LWWN8>SH1@T98C2X+8))^^Q)I1#K#H]
M$8I21T\DGC6@> # (\&-+,2P!8YM*-$I'#)\4"KJ"9_9FX"/;&*WA0]L077\
M/;TK-R2WSV^VT*?5MBRFWMW6JKIPEVCPR5Q'F[RTL+)S7AF&-JM56SUXF<.
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M.FVQ.#O$XAM!H.(6)T $PIX>8/=F7M_?_S(3'Q^0/"[/#QP\MMHMV)(&?X)
MK$"^85#4_IS?-,H_O?^./GRZNOKTEW__UQ_9D0'OX);A<B]_RDX(\-B>O4G$
M9!?FA=#0G<<VQR<D8EO<:4\OP6-O&I<-.=$8IM8FQ%;+_2Y$H0AH[ #M')=(
M-D)-=04Q_WPJNTW[C+1L^[C)4-MN(!>(A+R.6"+>:,!G1S/@LDWD)@,^WMK:
M940'FQ7 2LE5]$!_%VX3%?KQ-^I^/P5DC2/AS.=82Y_U.1,M@ZW@Z1OE8)NT
M2SMAU@(-U;(#BG1HV+MH%$3L<&%QBS..4R^(^+9HTEYE8-N4:JN*.%=)^].F
M/,C(U?!B >RX8V4&8G84QP#WFY;8'R@DT?J4U70MSP<&?E'6E?X$FV!'(QL_
M8YL.V1+';A>^\"!_?\EE=4:/V5L$_X>14(2SF"QQ<821?9$B!DK0AX=*[PUK
MQ62-?6NE:Y_0:\6T'P$MEE3U%?9;=#7]0A-U=2.\SC W< PGU^N52*$",1V'
M/JSAYJ81:QV!KX!X_S(M9V%]NL"99:#'$9Q:.8;+H-D4I[D@)GBG.S@$CX;N
M$TD[OU'\;*C OS ;?W[X!3C?[!9OG6C*Q(_C2,763"BU[#30@>_LT >13+)X
M;%_A9)\D'B:9/X?>=_*PI?_\)63U;CY08WYDH1JWD(5I?^%UZ8KR.5QR6:0N
MPL]E@9<UM2Q)4>K%:YSFQ7!B=H*8GSYFYV6R:J$\.2EJUC#3Z!=DF]_JCXL3
MRUOV_:*\W$N"?"_C7V5!C5Q&.!F[1HLSWMO/&&JN0<T48DT 4T375YB: QL[
M8>RV;%#7!9(BUOQ.[J >?GGUP>*(G ?/!D<@_6CYG]RD221^W>8-2GV:ZKT3
M%091KYBHD\G<7JBXO_+<TGO!,7CFUB4>(',3BQ_+!8JLF53FUF&@$Q\HU:>7
MN1F] F0:T%?LA>GF@N53/$!Z8>'17[O+A>?;&+[\OZMJ,]..5PRI+G7<4%>Y
M($GPFC.I3AY".&L5]N%\M4@3B*^6?X6I.93Q,ZDNRP9U)4"95.$H:J[D]0=H
MHW'>028U..E'S*1D)DTDD^HR;U#JTTSJG:I0F'K%5!WQ8#/]GR4S\ M>Q)D7
M,PO_!IA,F<CO=2!:2_YPAZ4US!DWGS*P$.BHM:Y"VXQ*G$1YN7H6(Y4&L$#I
M;_5-CU7^=/]=F4'E=Q.PF"M( W:+1)&6<1-HRTK6Z?7]]]>4;ADQM=_!<4-R
MV)PIUU#5\[RY]I>8G-,9HWJ#@6G#NIM>6==<YDQ>=]8U'>J#U),8G?M#9EZZ
M-HV5>IG8-ZP'>,W)UW08"Y%^C<_801*P1&AB8IYIZ0M2I%0Z@EQX,K7>P9(D
M;5.,G9.F9( M@(EL#V"B\9IIHCF* <95_LT,;7I^3"U3Z;!TS1J/@&X3!GT;
M'%&O*P5(9#E <O(JXOS!Z6,8N0_&'T>QN)[R 8)N?4,<L>B5A-&#$\(P,!Z,
M$!/9MS7?Q4%(!?Z;LR(/2@W6N[<Z-(SSYE5JT(3V<*EL=/ "MENE?@".O^\\
MOOYGM*VK6=F!V\(6#?^MOJ<KO[RZ59G*I\J");\WFKV5**^KYLJJT@PA60>^
M%U8G:B8:SD/0U?XMLA8_H-XC2Y4!O$I6?)$)>I^Q-WPIC1O:[X!L^ZIYDV.J
MKS"Z+P#?_S6:,QAM%UBG59/8"*:T<&B7D-=0^+>CK*$P.J7!]XF-1FG0#.X^
MOUKT"QW>"Q+Q4OI,YT66I&2+XT=J=.*Q4]O171P<^(B>O8LA,.YMX\D,E8%G
M3/WT2UU0'W&\7/[^NDS*\R18\K)N--UA"<X%V=(,YZ6\7XLF'4&"<!BL@T6(
M&:S9 W4=_?JA?R;NR8L#CTEH:!PY4^D+76*/IZ8',A14>9=>!@S,()BHOZ=B
M2.Z<L64"W@LQ^*"R7QYVESU/4*TOXIW?',@EH?. *+<,>7MH! QG>VJ'Q#H-
M0^LPWKU)&$O"Q0%A/)&%^O_C1?6-,S>$SN9ID  OUFMIL5ZP5V@9)U'N-&I"
M"_<Z=CK(F-5JA]Y!4YK0?2A[_LO%Y?QT?G?[P?OQ])HWJ#ZZN+JZ.KU^M4OU
M>F2US^>UF0&5TG<J!$CK-;[01'W0V,OW6@:.X7U EO$++;6S!)6/>>WK?I/Q
M%>!+^J,[B]&6]I6636)Y7\O*,5P&NX'MG=ZN('<T])Y(_G?KIV3!"SCSEQ'W
MQ-]@X.1/K<(Z\^M2,8X3E5LTH9Q/::0#_ZG0Z>;^G:]DM=IZT>FUA[C"?+\6
MB]^^_%0^K#V]3I<_G7 %K*(Q30%?\@?LS0<JOL#!)J_B:/@G=C)<?.T@S2!W
M(3?Q=(N7['CY\O5O[-)@M_W\H,<FJ+E!K@U@8E!]E2FZJ['30[5U@SLJD,2P
MX4JXH\K]SVL/&R?@$\#SP1&=PFB98+=9DT@#U28.[AJJFT=9+, C@8O]Q/^M
MG/@_EW<DO),=#HE'0/:)Y(7E%K6/KK)"E0*PXSN'"L;=,=NV9T+YH,)$AQMF
MA1JGGPM6&_0_UC/!*NG+3_9\S:*4VIK6KY@_8;OOOGX^00NON,.UMD'OAT1X
MD>NK31&55(?;&]Q%+NB=P6U=@!N#Q5]C>GYK[,109=O '@OVT,_'8TH)1_8!
MSD[\#.P$1C_O(S)J$HF@RL"!70%- AOS?I'NO?,8"&JOG,>'6=X$>/S1A,=/
M.%Z0P9G\<7@F?Z1YR/L4#(BN5T[=CR.>SYLOBUM4[0[J'8CI=V*O)F; $QF5
MUK'/\+4-@3JDT92;G^HK/O)"DP-^RI-\])F7LD. 5#Y>EHLI:?MTR.LZRG<(
M[I[G1(1 LSHO4DGL>W"D9=)8K!OEW-^!!4[XUOLDX FJY+S3!>B8("Q?ACTX
MV% ]W@G" S.<L(9FN]^"$-.6$48[[R5?>L]G(;;N12>M. W^9"O=[.;Y';M&
M?LGF,/HOOJX?O;(SB&Y8 W,J$98U0Y:CN,E8D'V[NMNCXG81!FL>MB3S](H/
M'_WW[:KL;A8(6RC0"Y%[*7#HE7K8,W18W=_$OJZLKT8>BD>\<\MW(;+OC[R4
MA]%!*86U]5BTSB5-.YBV(8BF![2$I)%K[*%+UVGV_AK38_L@X;R%;0/S7#<%
MN-'Q! TO4/J =Q=@A]-7[@/<)B(]C1HN1;$P<&!/P([RO9-\6)+WRX&F1_*)
M[./\1K&RH:#Y5_:5YF'T$GK;NXU'OX>/LY35ED[H%P#>V]E'J?5^3S.E8]V=
MK6_CA/:%]C#;R47;AE:XV3]::$8MU2=5#7AN)V*&=I>0N;^9!TQ[[.VXD-=[
M!K 7WR%N#>_')KBKQ/7U@UPP;OIU7X>3&WL3:1][)^#>0#:;UGR5AG-[[3M@
M7HF? M^L.G%'-=JF5E-#)['1M8_1$W!7-)<NG<N[&QD6K6_$C8SQIO(![SSZ
MU;!X<:#?RTD]F6;O(U4R!UB/[#9AK+>.6E;9+CMJ*&F]6TR*'M)51^7>OM?Q
MGE$3ZX9+COI0Z[7(V"W>=%U1Q]A)T'/0UX1ZYK@GIOG+0!5UWWFI@[%70<QA
M7N2I[1C^W9V>3>[IV7A#]\X\" R]"N:!QOJ_[N@(1>E=OF_U'ON8IBK+%F.[
M&Q4_FJR1C9<0RP2/ESO52(G<T:MU'566MRQW!R<H+AJC91;S5S$;7&X,GGIP
MJ\ "T1ZY)M?$[2OR=(ES S"8B*];?@]HT9CLUR::*C"]<EQ(PI_>P+ ,4.2"
M 2..;B4]X#$[6GA(YNC>\ "=1<O)NUK,2_C47G?@=UZ<1@?[3,P[%E_?I*,-
M#?3U@,_*QJJE?#&4U%J/ZKPQYW"BWN621IZF>P"+6 UYDY;Z,BJJFJH=#M4P
MH8"Y3B \G]7SQ!J8.7Z%V'TCT)5$',ZQ:QF9F"D#C%;,%0,A>"9&\!N!J23R
M<0Y3T CI,UZD#]BGZ6X:X&3^Y 4ANS?Y"XD?O!#/H^7E/[,@?=DW^?)T$_P<
MDR3Y-8HQWS2XO*9_M0@!+;;XB>'$VA =R@KPR S8,*F7 -5S_DA2+V0>Y,/9
MCRBK&J"0MF#[P3R??NTLY!6J"=N;RB^MB/&&O:A_XH<:R1:C#_/;BZL?6=G2
M('K"27[#!>V^I,:B)#?E!6VQEV0L5/12M/*"&#UY88:+.7?#-@*P/K4G-$TC
MZX@;1!]TZ??*W^%T1>+3A/X2/_(];Q]FAU_KP$K,?S$P.R.<5G9]^<_3FZL?
M1XY[P1T"<4C&ID.'TE"Y>UB3I^+)8*)Q:(L&\6$TDF?BT+[Q"9H?> /N#'*I
MC9:<GR>(RT9[X8A)?R>M/NY>$6LM,PU(4_3RD'_/:1OA-9N&I9D(M&&#L)=F
M,3GW6I,T?F>? 7Q>$?LFET#][ 61@P2J+A8P@<K%CNV_F!633*!JACEU7Y4>
M:0*UIBV.,('B7^L]@;)U")"S09N,\),!TP Z&>Q-GHHGFTX"5;=H$!_F)H%B
MTM])JX^[5\3:"210I2F +W*@S1J$NZ+TB4W11Y ].:>>P^S)&?7&SYX@4B6(
MO&@$'S2-C,=)>B/(92:8A^PW#[^G'_HDL_*=P(F%G5,<*648.3]PDPP 1?YO
MFAB0P;L],\8(RZ<0@[L)N(OH^C))@RU?O-M/%V\:\Y!1LSWFQX^'+TC2KCEO
M+<<F+L[E#.X(F-IIQ,<U2V ]0B6X&2?OK[+P:8/#X'02D;/8M/>X645$*W?9
MY@2 QV0B[;SFWJC1?,2(L73=!#?> 60UG0E[IPYPA W'G3$B[5+WV-%VW0XW
M#)JQ.I;O^.\J?CXR_D&C[KT*=N[BFY?R6.1V]8W$^)$&';<1_COV8F%%\EY]
MBY_2L*\-X8U4@4?1?;1+F6TNK%ETNPH_DTI0'E]Z-!S]OL,^2[6WA5@6L=+H
M&K-K2=FN$XQ>J.R1@\I^F".V4&@Z ",Q%>E[*!\4]C"!82^U<("G >!#"]O?
M:GC^5N&9]D2LZT3*GPZ,:TED-Q"P#R,X!S-8H?4VOL9)8C1_=?14S%["GBY(
M+% TV,PEUVU,8YDHRUFKG*L0B5%()4]TSNK"F8K9"@#HT5H@1$EJJ>(!8>YV
MINI0"@5PQ2Q5S4T4OZSCQ.<H!S@VG)\ @0PZ-\FJ;2?"<MO)?)&(;M&UE**X
MRDDIQ<5E  JE<"2W-,"X4K^67/E-(8GLJA#J TH9$RW4KXM&5>5]$VCHE=)7
M2%36QM>S"+!T%WGRXC1(KEAIIXC'9UXX_UD8PVJU+0MT=;>U*@#3)1J^#)>&
M-GF=%V7G\[():K1!\Y\1_<Q##\\!G9.W69@&U;-=XR8$_H[0BU[0PDORMW.?
MZ#_"$]8U_1/'U++EV-6XM(!#3,>W51"FJ]N^!HQ:N%-L A73TE'3'Y5G7;"<
M1GP(#"E9+2P83-E6O%+)ARQRI:.K/[)F-60=)9!DU:I@@ 3Z.N930-8XDET!
M*WE:?*V#IS;X;@D#G\+%\J4@%C4_SS\L+OIDD3.:;W%,Y]^H-3DO I)B?Q.1
MD*Q?RKEYY/E7-I9$/0!-&+<:5L 5"@"&!,S,*1%L H:S)AJFX<9Z#+%DSC,8
M8\MY32 1<":32#<9Z5DUTJ]VD"7SD<$@@\XYMSO,4MYH?8UIDG(?K#?I[>K7
M!,^3!*?S?']EPX\7>#'N5WQ=@WXV2-96 SZWF6J6PM],T/F\.J#EU9[Q5R11
M@I&7IG&PR%*VTX2!*V;R3LGJ-&,/F<C\3B52:D4A4SOR/&F.,F(#@"8EM454
M9#54.AC 869J8Y4PT*:S>]4>\0XGZ+Y$+^V$>*\35._W)E K"1<<P]8RQ##2
M!1A\&.N% >^,.^;]3T[=<\/SMMQM[HE'KB P$'PE@9!C^((&3\4U'LDCF?O_
MS((8YR\*,'MG<,N.BW 3VC6B#7L5/X]V+QMV:BH!#YK,]$JI:2*&7ZKA>\D&
MD2Q=A>09K4B,/-8O"4JNAD5__F(N/P"4,Q1%),T_> XH;9=X%43Y6C^[@"/U
MOI.(;,=>93 %&NF/@B:'-054##92.!"^86(F0X40R*;Q4MF:_<!%>W1=AS+O
MD@=.(T\V V!4$B<Y!*EEC&2@";2*K:%>"+"R^$C3Y9ZP0XY'#U9)5.00K* 1
MT57DQRP*^XSS_UY%<]^/,[RD>C_C%8YCBK_ 6P0AWY350G_/WL5/9=S;AJ.&
MRL CIG[ZI93M(XY'4$'1$7U8%EU_K%\B&N,=B[_I7\5UHD6$Y*W7,?=&M<)"
MQ5(5V_3K9TPA6F0I#[1>,+L^,%ARG[ LS*&>HK*'JLS/2@=18__O/KWR7_QP
M[-6LOO F]IAK>A-#0957Z67 P"R#B=MZ*H;D%XWCKBIR?:[(11%>=.5L*#NC
M6N\WAW))A#<@S"TCOAX: =?&>FJ'!#N/ W-4U]UZP]_'=#Y\<]"6Q(,#0AOV
M8EH277C)YL+;!:D74J5W- :(TDLV]2^#-(L/8D*#'M5.5XT>=MN_E H<['K5
MU=FQ%TQ/Q/F7C/W17!RC -IY+WR-;$=_EXW' C4:M*V"[VPFRK,/1M<=%YJP
M<Y8IVGA/&"TPCJJ8;O2-K_IH(OV&N[W/3-FYMMM,4]$ X(7:%JNMS!:V?(ML
M=,I!6[3E>,Q;HWKSHX6@=-,L. :M-]!J:0'=1JNMT1:)LW(S1L)N(.$Q#7.;
M?@V4N9/,,]YC!Z5T RXX*$$CE7N<8/K#;7A@](1#LF/S\SW]9Y3A7Z,ECILG
MAJJ30<+-NT#2BI_06IH-=RV5@T=&,/9(20\A_KQHGF^QB@N)1793R40)CI\"
MG^)^AV/J,;;4<61, ?):UZ)75TZ/'$U!H9K 0ZOI;"P%5XX(Q,"1R0<3V0$9
MXI)V9XQW-:K5Y*"2D%P2:IW(K1V[G<0NXPG23!)I3HAGEA$J@ 6 T2N0-2[9
M1J/>^W_QMKO_^%R1ZYT]*F1,ECV'H?30[/EHPIXG'"^(6_Y\=,R?CX?\>9^<
M+*$S67I]A,Q4]]4IBKT=]^3%"]GRO3 5U6U>_'CJYC:.0B4=/%O45"AENE;_
M9KY7[&A"*]S8U127'4\0_NZ'V9)M4Z@^S+NRK1*\9C59H8>[JYO[^7_-1\[Y
MM.%#>@QQD["JGA4C]52XQBE,8J6KR0JA-#7:EQG:;PBM6DYD;G&"-4GJ @HV
MR^1#1X51=J&*CW056H%NU@6ZEXEE#4Z@)XG[0:%G&;GKJ# *S;L36UUU5L#[
M^(:]G206!H4<:#1;ACG=0:RB55FI5];*JERI6"AXI-JM1UZ,M*/;>>EKX]S7
M=D29Z$.4T6%GY(W&ODM(-=A$?V1:%47%'?;50[L$.L(04'G;;@5]T,/*UI;@
MF)KK!$"(K.AL?XA8!H$=D@%7EA5:^@!E=MQ D01Q%D !W;=P0;9;'/N!%PHG
M3MGCJDYP^[%= >"F-#C_)I/<4;)7U.%\__%$ "H='Z+SF[9+XC:;UFK="F5
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M?T(TK$\P\FA\[OD^R2)>7H3Z.1JWK[P@1D]>F(T=D<-PA$!#M>GLK,16K@[
MN%%I#!.'@YCACL!G=0:74DZ9&%3)V1/X<D_>ZL;%4MH[KT38F22Q+.-N:_V
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M&P!!K)KUZ[_9-?T7_;#\B/X/6RX[__]02P,$%     @ 1GUF3Z?]<-M28P
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MB-/K> /1+I\.+D :A%$B;S.F37";WG_ZZ=/'G_(6"9@9-N\<1E'P!/%T&;Z
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M%*[VM$@0M2'=9E#V])\]Z>G+'4!;O!SYC."W]%EDP864K9[G4+J* !7!E)#
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MPY23<5J)MM2IA-9]T.@(JPD@"6M_#R47JU6VRR(RA_/.>]C TBU7@4R]G >
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MU(5#TF4\N;U7]%KKXOJD_-8&P!C3<\W@XE.,E"F<ZV\X[SWU<)?FN-S?4.]
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M%MNF!AGL_%6B=*Y0L8.*<P:'E?FQI^6YH_<^IG,HS=G+\ ZO!723R7B'X J
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M4KC#II.Q8. 35,&<#()11;@-=GCIUFH&<[$@I2L%$M#9FU(*_PC>W0OG:]G
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M@VB-98^ZC2#&R$[EGOO1%DIH2WP/8O MB!X!VC%1+J5N 5A [0$V5675A9V
MK^?IOECR$<&6&_*2('=B4"D@P!5=P#MH"27NARZ:]63.M\+IN-WF.X!"N%YN
MKA @HT,%,[PB M1TBWB'&XG4_9#393Y9-BP-["RB"'XC(>UX#_T(8KS5N-[M
M$7PI9G<%)*DQ$.!*QL [E&EII!_F9%5-YE6K@<#K.$S#(+H!:4I6CN>XA6'Z
M"/,HB&(/MWR*PFVN(04\FK 3H%./G7=8[:&M?LC5JW@(CS[;.%8291D_/H=H
MO8CC\ 6W+$"'Y89,%N=PAX?L*A^W%T'*WC&/4)]@)%BNS[NA,J2^^XTERRTS
M>)/<U<%V%6[2YQ$'FUY]_0>;:GVG.MB,]#W*8%-M63G8_NSI 09U-!-NG]/E
MYFM2.(/3%Z4JM-7EJ)C6:3SKR*F.10G7$D<_GP2.ZF@?(8(Z5$SL-*@\0@U/
M-E.\-/B52/GD;?Z!MF2_ C(4P'J!6Q=LP3T@M\_-T[SW0A"I%V>B2Z6X1[#3
MUH8I'E4JJL[V?;TN$DI,E 2S.(^&+N.@=7 J**Z"4V9Q?W$JUX8EG#(KJG#J
MZR449Z8XSQ"2H9)'+)Z):V*/$">1M/>\7+.MT.1KNA?J4B0XL"X2Q$1,]!R)
M/$(-1S)3M!S952CQ]J45YB@(\^P-Q0L0&<\WRJ2HT![QBCKE%5 ;BD93;\%K
M^O@-1"_@"XS39Y7;.ATVHN,I)3:3#50CB/!.HO0UUA[>.HWA'CHI->($W:M8
M@O\3!.CQ&S1$.U5:$^1UZ9/%-EL_XT"ZKOL$W;JX\N**E6X@5,J;H+DH?]IX
M9NAH1$07M7N>QE%'XBN8T5%2IL4-$%T4/VE ,S0T'IZ+RCU_ZE%+X/"ECX5N
M%C>!<U[\M.'<U="(<,XK]SS_I*K BPUN;D],,WEH IOB<;+H%NEJ'(A3+9C,
MDVY<G!M"VQ#-)PS@23#;RP?-A5S50D&_QNOR&@FL+U]7F'2Q(__2P:R,APJ
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M"G%C"$MR%E;L 2PG E*HHW<:(&$=;RL)D+JZ)TP!)&RDY\N,.0'022U%Y@1
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M,%\R+FAT;5!+ 0(4 Q0    ( $9]9D_8C'S0#I   ,(%!  *
M  "  3LC  !E>#$P7S,N:'1M4$L! A0#%     @ 1GUF3TR@MI 0"0  ^#,
M  H              ( !<;,  &5X,S%?,2YH=&U02P$"% ,4    " !&?69/
M E?@URH)  !N,P  "@              @ &IO   97@S,5\R+FAT;5!+ 0(4
M Q0    ( $9]9D_HQ$]4N 4  *\9   *              "  ?O%  !E>#,R
M7S$N:'1M4$L! A0#%     @ 1GUF3PPID]-OT ( ;R$I  L
M ( !V\L  &9O<FTQ,'$N:'1M4$L! A0#%     @ 1GUF3PB=ZGLI$P  5]L
M !$              ( !<YP# &EO;G,M,C Q.3 Y,S N>'-D4$L! A0#%
M  @ 1GUF3P6,,#\E$P  5!(! !4              ( !RZ\# &EO;G,M,C Q
M.3 Y,S!?8V%L+GAM;%!+ 0(4 Q0    ( $9]9D]GCBC\LTP  $NB!0 5
M          "  2/# P!I;VYS+3(P,3DP.3,P7V1E9BYX;6Q02P$"% ,4
M" !&?69/6[DJUC;,  !Y>0P %0              @ $)$ 0 :6]N<RTR,#$Y
M,#DS,%]L86(N>&UL4$L! A0#%     @ 1GUF3Z?]<-M28P  BET' !4
M         ( !<MP$ &EO;G,M,C Q.3 Y,S!?<')E+GAM;%!+!08     #  ,
+ -0"  #W/P4    !

end
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>70
<FILENAME>R46.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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6807778704">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Roche (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="2">9 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Mar. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Sep. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 167,892<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 145,395<span></span>
</td>
<td class="nump">$ 628,918<span></span>
</td>
<td class="nump">$ 407,559<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 72,193<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 62,639<span></span>
</td>
<td class="nump">$ 376,833<span></span>
</td>
<td class="nump">$ 225,584<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 56,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 56,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 72,600<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">3.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">8.00%<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_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember', window );">Roche [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 4,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,800<span></span>
</td>
<td class="nump">$ 52,300<span></span>
</td>
<td class="nump">$ 5,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember', window );">Huntington's Disease [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">$ 220,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 220,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NextPotentialMilestonePayment', window );">Next prospective milestone</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfCollaborationAgreements', window );">Number of collaboration agreements | Agreement</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<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_NextPotentialMilestonePayment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 milestone 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_NextPotentialMilestonePayment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfCollaborationAgreements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The number of collaboration agreements with the collaboration partner.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfCollaborationAgreements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_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://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 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=118260190&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 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118260190&amp;loc=d3e13537-108611<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 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>num:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=118944033&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=118956577&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=118944033&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 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130543-203045<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 5<br> -URI http://asc.fasb.org/extlink&amp;oid=118956577&amp;loc=SL49130545-203045<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_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementsAndLicensingAgreementsRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2013WithRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>71
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6637443520">
<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>
<th class="th" colspan="2">9 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
<th class="th"><div>Sep. 30, 2018</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized from amounts in beginning deferred revenue balance</a></td>
<td class="nump">$ 30.3<span></span>
</td>
<td class="nump">$ 37.2<span></span>
</td>
<td class="nump">$ 103.5<span></span>
</td>
<td class="nump">$ 80.4<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=118956577&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>72
<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;">v3.19.3</span><table class="report" border="0" cellspacing="2" id="idp6665364928">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Segment Information (Tables)<br></strong></div></th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr><th class="th"><div>Sep. 30, 2019</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock', window );">Segment Information</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 show our segment revenue and income (loss) from operations for the three and nine months ended&#160;September 30, 2019 and 2018 (in thousands), respectively.</div>

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

<table cellpadding="0" cellspacing="0" id="z0ad30f1f4f2a4ba8890de9668d5998f8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81,672</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81,672</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,945</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,945</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">136</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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;">2,082</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83,618</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,081</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">95,699</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,165</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,543</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,515</div></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;">72,193</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">152,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,624</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,515</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,892</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">119,147</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">53,215</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,993</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">165,369</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,636</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,591</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,478</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,523</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="z1fe532a6dd9c40528713d7c7fce08810" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended September 30, 2018</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;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,010</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,010</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,746</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,956</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></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;">82,756</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,105</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,241</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62,639</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,061</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">19,241</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(51,907</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">145,395</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87,664</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84,249</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">163,967</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">90,397</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(65,008</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(43,961</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(18,572</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="zc3a76d4662b34f2ea78dc5e6136dfb77" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended September 30, 2019</div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,884</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,884</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,563</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,466</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;">6,172</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,638</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">220,350</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,735</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">252,085</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">294,512</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,328</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(94,007</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">376,833</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">514,862</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,063</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(97,007</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">628,918</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">355,437</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">256,152</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(87,900</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">523,689</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">159,425</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(45,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,107</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,229</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<table cellpadding="0" cellspacing="0" id="zcf2b13dc1bb64910b74499773f3efba3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Nine Months Ended September 30, 2018</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;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td colspan="1" style="vertical-align: bottom;" 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: top; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,743</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">167,743</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,432</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,232</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 43.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">177,175</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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,200</div></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;">181,975</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; margin-left: 7.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue under collaborative agreements</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">232,850</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42,670</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(49,936</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">225,584</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; margin-left: 25.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total segment revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">410,025</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,670</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(57,136</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">407,559</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">279,084</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">213,428</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(12,796</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">479,716</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130,941</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(158,758</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,340</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(72,157</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table shows our total assets by segment at September 30, 2019 and December 31, 2018 (in thousands), respectively.</div>

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

<table cellpadding="0" cellspacing="0" id="z6c5c599a255e4059847439344a157872" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Assets</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;">Ionis Core</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Akcea Therapeutics</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Elimination of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intercompany Activity</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">September 30, 2019</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,233,175</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">383,167</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(721,353</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">2,894,989</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 52%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">December 31, 2018</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,975,491</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">365,261</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(672,968</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,667,784</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<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_ScheduleOfSegmentReportingInformationBySegmentTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 profit or loss and total assets for each reportable segment. An entity discloses certain information on each reportable segment if the amounts (a) are included in the measure of segment profit or loss reviewed by the chief operating decision maker or (b) are otherwise regularly provided to the chief operating decision maker, even if not included in that measure of segment profit or 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 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8736-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 25<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8813-108599<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 20<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=108376223&amp;loc=d3e13816-109267<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&amp;loc=d3e8721-108599<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -URI http://asc.fasb.org/extlink&amp;oid=115929826&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_ScheduleOfSegmentReportingInformationBySegmentTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>nonnum:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingAbstract</td>
</tr>
<tr>
<td style="padding-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>
</SEC-DOCUMENT>
